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Lin J, Wang J, Zhao K, Li Y, Zhang X, Sheng J. Molecular targets and mechanisms of traditional Chinese medicine combined with chemotherapy for gastric cancer: a meta-analysis and multi-omics approach. Ann Med 2025; 57:2494671. [PMID: 40317214 PMCID: PMC12051567 DOI: 10.1080/07853890.2025.2494671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 01/23/2025] [Accepted: 04/05/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND The combination of traditional Chinese medicine (TCM) with chemotherapy has been widely applied in the treatment of gastric cancer (GC). However, previous clinical studies have been constrained by small sample sizes and a lack of investigation into the molecular mechanisms of TCM. This study aims to assess the efficacy of TCM in treating GC by leveraging the strengths of meta-analysis and multi-omics approaches while also summarizing the underlying pharmacological mechanisms. METHODS A systematic literature review and meta-analysis were conducted using online databases to collect data before May 2024. This was to investigate the association between TCM combined with chemotherapy and the prognosis in GC. The molecular targets between the high-frequency TCMs and GC were identified through network pharmacology. The underlying mechanisms were investigated using multi-omics. RESULTS 9 studies with 2,158 patients were included. The meta-analysis results demonstrated that the combination of TCM and chemotherapy significantly improved the overall survival (OS) of GC patients (OR = 2.91; 95% CI: 2.70-3.12, p < 0.00001) and enhanced their quality of life (OR = 4.00; 95% CI: 1.99-8.03, p < 0.0001). Network pharmacology analysis identified 13 potential molecular targets of TCM in GC; additionally, multi-omics analysis highlighted the significant roles of MK, MIF, GALECTIN, and CypA signaling pathways in GC. CONCLUSION The combination of TCM with chemotherapy significantly improves the prognosis of GC; future research can focus on these key molecular targets and signaling pathways. This supports the application of precision medicine in cancer treatment and suggests the rational use of TCM in managing GC.
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Affiliation(s)
- Jie Lin
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Jincheng Wang
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Kai Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Yongzhi Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xuewen Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Jiyao Sheng
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
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Fang Y, Pan J, Wang P, Wang R, Liang S. A comprehensive review of Schisandrin B's preclinical antitumor activity and mechanistic insights from network pharmacology. Front Pharmacol 2025; 16:1528533. [PMID: 39995410 PMCID: PMC11847788 DOI: 10.3389/fphar.2025.1528533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 01/21/2025] [Indexed: 02/26/2025] Open
Abstract
As an active constituent in the extract of dried fruits of Schisandra chinensis, Schisandrin B exhibits diverse pharmacological effects, including liver protection, anti-inflammatory and anti-oxidant. Numerous studies have demonstrated that Schisandrin B exhibits significant antitumor activity against various malignant tumors in preclinical studies, which is achieved by inhibiting cell proliferation and metastasis and promoting apoptosis. As a potential antitumor agent, Schisandrin B holds broad application prospects. This review systematically elaborates on the antitumor effect of Schisandrin B and the related molecular mechanism, and preliminarily predicts its antitumor targets by network pharmacology, thereby pave the way for further research, development, and clinical application.
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Affiliation(s)
- Yanhua Fang
- The Key Laboratory of biomarker high throughput screening and target translation of breast and gastrointestinal tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
- Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Bioengineering, Dalian University of Technology, Dalian, China
| | - Juan Pan
- The Key Laboratory of biomarker high throughput screening and target translation of breast and gastrointestinal tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Piao Wang
- The Key Laboratory of biomarker high throughput screening and target translation of breast and gastrointestinal tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
- Department of Oncology, Central Hospital of Liwan, Guangzhou, China
| | - Ruoyu Wang
- The Key Laboratory of biomarker high throughput screening and target translation of breast and gastrointestinal tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Shanshan Liang
- The Key Laboratory of biomarker high throughput screening and target translation of breast and gastrointestinal tumor, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
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Yuan C, Wu S, Wu Y, Tian C, Wang Z, Zhang X. Effects of Traditional Chinese Medicine "Fuzheng Qingdu Decoction" on Autonomic Function and Cancer-Related Symptoms in Patients with Advanced Gastric Cancer undergoing Chemotherapy: A Controlled Trial. Integr Cancer Ther 2024; 23:15347354241229414. [PMID: 38323452 PMCID: PMC10851715 DOI: 10.1177/15347354241229414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 12/16/2023] [Accepted: 01/15/2024] [Indexed: 02/08/2024] Open
Abstract
OBJECTIVE To evaluate the effects of Fuzheng Qingdu Decoction (FZQDD) on the autonomic function and cancer-related symptoms of patients with advanced gastric cancer undergoing chemotherapy to verify its clinical efficacy. METHODS Sixty-two patients with stage III or IV gastric cancer were included in this study. The patients were divided into 2 groups: the chemotherapy (33 patients) and chemotherapy with FZQDD (29 patients) groups. The primary outcome was the autonomic function of the patients before and after the interventions. The parameters that were used to assess autonomic function were deceleration capacity (DC) and acceleration capacity (AC) of heart rate and heart rate variability (HRV), which comprised standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low-frequency power (LF), high-frequency power (HF), total power (TP), and LF-HF ratio. The secondary outcomes were cancer-related symptoms and the quality of life. RESULTS DC and HRV parameters (ie, SDNN, RMSSD, LF, HF, and TP) were significantly decreased in the chemotherapy group; however, AC significantly increased after the interventions. No significant differences were observed in the DC, AC, and HRV parameters before and after the interventions in the chemotherapy with FZQDD group. Nevertheless, the changes in DC, AC, and HRV parameters (SDNN, RMSSD, HF, and TP) before and after the interventions were statistically significant between both the groups. FZQDD significantly improved the cancer-related symptoms and the quality of life of the patients. CONCLUSIONS Oxaliplatin combined with S-1 (tegafur, gimeracil, and oteracil potassium) can impair autonomic modulation in patients with advanced gastric cancer. FZQDD can alleviate autonomic dysfunction by increasing the parasympathetic activity and decreasing the sympathetic tone, helping patients restore the dynamic sympathovagal balance, and significantly improving the cancer-related symptoms and the quality of life of patients.
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Affiliation(s)
- Chengjia Yuan
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Shuang Wu
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yang Wu
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Cuiling Tian
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zaichuan Wang
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Xiaochun Zhang
- Clinical Traditional Chinese Medical College, Yangzhou University, Yangzhou, Jiangsu, China
- Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou, Jiangsu, China
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Xie W, Zhang Y, Tang J, Zhu X, Wang S, Lu M. Efficacy and Safety of Traditional Chinese Medicines as a Complementary Therapy Combined With Chemotherapy in the Treatment of Gastric Cancer: An Overview of Systematic Reviews and Meta-Analyses. Integr Cancer Ther 2024; 23:15347354231225961. [PMID: 38229425 PMCID: PMC10798087 DOI: 10.1177/15347354231225961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 12/23/2023] [Accepted: 12/26/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.
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Affiliation(s)
- Weijian Xie
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Yunsong Zhang
- Digestive internal medicine department I, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Jingyun Tang
- Tai’an Disabled Soldiers’ Hospital of Shandong Province, Tai’an, Shandong, China
| | - Xiaolin Zhu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Shijun Wang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Meiqi Lu
- Digestive internal medicine department I, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- Postdoctoral Research Mobile Station, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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Fan L, He Y, Li Y, Li X, Liu D, Wang R. Efficacy and safety of traditional Chinese medicine nursing intervention in postoperative patients after gastrectomy. Oncol Lett 2023; 26:537. [PMID: 38020302 PMCID: PMC10655047 DOI: 10.3892/ol.2023.14124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/04/2023] [Indexed: 12/01/2023] Open
Abstract
Gastrectomy is a technically demanding procedure for gastric cancer patients that is associated with different degrees of postoperative complications (POCs). Perioperative traditional Chinese medicine (TCM) nursing intervention presents benefits for improving the survival of patients with gastric cancer. However, the effects of TCM nursing intervention on POCs and the prognosis of patients with gastric cancer following surgery are far from clear. In the present study, the effects of TCM nursing intervention on POCs, postoperative physical capacity, metal status, long-term survival and recurrence were investigated in patients with gastric cancer after gastrectomy. In total, 1,032 patients with gastric cancer were included in the study. The patients underwent a gastrectomy and were randomly divided into two groups: The TCM nursing intervention group (TCM group; n=520) and the routine nursing intervention group (control group; n=512). Postoperative pain score, hospital stay, POCs, postoperative gastrointestinal function, frequency of postoperative symptoms, inflammatory index, quality of life, physical capacity, mental status, survival and recurrence were compared after gastrectomy in the TCM and control groups. The treatment-related adverse events of TCM in patients after gastrectomy were recorded in the TCM nursing intervention group. The outcomes showed that TCM nursing intervention decreased the postoperative pain score and hospital stay, improved gastrointestinal function, and decreased the POCs and the inflammation index compared with the control group. In addition, TCM nursing intervention improved physical capacity, quality of life, depression, anxiety, immune activity, long-term survival and recurrence in patients with gastric cancer after gastrectomy. Furthermore, TCM nursing intervention was only associated with a low number of adverse events. In conclusion, outcomes in this study indicate that perioperative TCM nursing intervention improves POCs, mental status, long-term survival and reduces the recurrence of patients with gastric cancer, suggesting that TCM nursing intervention is efficacious and safe with regard to improving the prognosis in these patients after gastrectomy (Retrospective clinical trial registration number, 2015001CW1; name of the register, The First Hospital of Harbin; date of registration, May 7, 2015).
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Affiliation(s)
- Lizhi Fan
- Cadre Ward (Geriatric), The First Hospital of Harbin, Harbin, Heilongjiang 150000, P.R. China
| | - Ying He
- Department of Ultrasonography, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, Heilongjiang 157000, P.R. China
| | - Yufeng Li
- Department of Thoracic Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, Heilongjiang 157000, P.R. China
| | - Xinxin Li
- Intensive Care Unit, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
| | - Dan Liu
- Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, Heilongjiang 157000, P.R. China
| | - Rui Wang
- Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, Heilongjiang 157000, P.R. China
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Chen Y, Li Y, Wu Y, Chen S, Jin X, Chen X, Fei B, Xue X, Wu R, Chai K. Yiwei decoction promotes apoptosis of gastric cancer cells through spleen-derived exosomes. Front Pharmacol 2023; 14:1144955. [PMID: 37324462 PMCID: PMC10267389 DOI: 10.3389/fphar.2023.1144955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 05/22/2023] [Indexed: 06/17/2023] Open
Abstract
Yiwei decoction (YWD) is a formula of traditional Chinese medicine (TCM) that is clinically effective for the prevention and treatment of gastric cancer recurrence and metastasis. According to the theory of TCM, YWD tonifies the body and strengthens the body's resistance to gastric cancer recurrence and metastasis potentially via the immune regulation of the spleen. The aims of the present study were to investigate whether YWD-treated spleen-derived exosomes in rats inhibit the proliferation of tumor cells, to elucidate the anticancer effects of YWD, and to provide evidence supporting the use of YWD as a new clinical treatment for gastric cancer. Spleen-derived exosomes were obtained by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. The location of the exosomes in tumor cells was then determined by immunofluorescence staining. After tumor cells were treated with different concentrations of exosomes, the effect of exosomes on cell proliferation was determined by cell counting kit 8 (CCK8) and colony formation assays. Tumor cell apoptosis was detected by flow cytometry. Particle analysis and western blot analysis identified the material extracted from spleen tissue supernatant as exosomes. Immunofluorescence staining showed that spleen-derived exosomes were taken up by HGC-27 cells, and the CCK8 assay confirmed that the relative tumor inhibition rate of YWD-treated spleen-derived exosomes in the 30 μg/mL reached 70.78% compared to control exosomes in the 30 μg/mL (p < 0.05). Compared to control exosomes in the 30 μg/mL, the colony formation assay indicated that YWD-treated spleen-derived exosomes in the 30 μg/mL colonies have decreased by 99.03% (p < 0.01). Moreover, flow cytometry analysis showed that treatment with YWD-treated exosomes in the 30 μg/mL increased the apoptosis rate to 43.27%, which was significantly higher than that of the control group in the 30 μg/mL (25.91%) (p < 0.05). In conclusion, spleen-derived exosomes from YWD-treated animals inhibit the proliferation of HGC-27 cells via inducing apoptosis, suggesting that spleen-derived exosomes are involved in mediating the antitumor effect of YWD. These results demonstrated a novel exosome-mediated anticancer effect of YWD as a TCM formula, thereby supporting the use of YWD-treated exosomes as a new approach for the clinical treatment of gastric cancer.
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Affiliation(s)
- Yingzhi Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Yu Li
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Yue Wu
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shiyong Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Xiaoming Jin
- Stark Neuroscience Research Institute and Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Xuan Chen
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Baoying Fei
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Xiaomin Xue
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Renzhao Wu
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Kequn Chai
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
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Sun DZ, Wei PK, Yue XQ. Xiaotan Sanjie decoction normalizes tumor permissive microenvironment in gastric cancer (Review). Oncol Rep 2023; 49:74. [PMID: 36866751 DOI: 10.3892/or.2023.8511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 01/20/2023] [Indexed: 03/04/2023] Open
Abstract
Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non‑malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor‑β from tumor cells, immune cells, cancer‑associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell‑directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.
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Affiliation(s)
- Da-Zhi Sun
- Department of Traditional Chinese Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, P.R. China
| | - Pin-Kang Wei
- Department of Traditional Chinese Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, P.R. China
| | - Xiao-Qiang Yue
- Department of Traditional Chinese Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, P.R. China
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Ye HN, Liu XY, Qin BL. Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer. World J Gastrointest Oncol 2023; 15:69-75. [PMID: 36684044 PMCID: PMC9850758 DOI: 10.4251/wjgo.v15.i1.69] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/28/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is a malignant tumor originating from the gastric epithelium, and its incidence and mortality rates rank third among all malignant tumors worldwide. It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice. However, with the advancements in medical technology and informatics, the values of traditional Chinese medicine (TCM) in preventing and treating GC and improving prognosis have increasingly been recognized. According to TCM, clinical manifestations of GC can be divided into Yege (dysphagia), regurgitation, stomach pain, and Zhengxia (abdominal mass). Due to the unbalanced distribution of health care resources in China, most GC patients already have progressive or advanced-stage disease at the first diagnosis. As a result, most GC patients have poor physical function, and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life. In contrast, TCM therapies have shown promising efficacy in the management of these patients. Here we review the role of the integrated TCM and Western medicine in treating advanced GC.
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Affiliation(s)
- Hui-Nan Ye
- Department of Gastroenterology, Cancer Hospital of China Medical University; Cancer Hospital of Dalian University of Technology; Liaoning Cancer Hospital & Institute, Shenyang 110801, Liaoning Province, China
| | - Xiao-Yan Liu
- Department of Gastroenterology, Cancer Hospital of China Medical University; Cancer Hospital of Dalian University of Technology; Liaoning Cancer Hospital & Institute, Shenyang 110801, Liaoning Province, China
| | - Bao-Li Qin
- Department of Gastroenterology, Cancer Hospital of China Medical University; Cancer Hospital of Dalian University of Technology; Liaoning Cancer Hospital & Institute, Shenyang 110801, Liaoning Province, China
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Huang W, Wen F, Ruan S, Gu P, Gu S, Song S, Zhou J, Li Y, Liu J, Shu P. Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer. J Tradit Complement Med 2023; 13:245-262. [PMID: 37128200 PMCID: PMC10148141 DOI: 10.1016/j.jtcme.2023.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 12/17/2022] [Accepted: 01/03/2023] [Indexed: 01/09/2023] Open
Abstract
Background and aim Gastric cancer (GC) is a common malignant tumor worldwide. Modified Gui-shao-liu-jun-zi decoction (mGSLJZ) is a clinically effective traditional Chinese medicine (TCM) compound in GC treatment. This study aimed to analyze main chemical substances of mGSLJZ and investigate active ingredients and molecular mechanism of mGSLJZ against GC. Experimental procedure HPLC-Q-TOF-MS/MS was used to analyze chemical substances of mGSLJZ, and potential active ingredients were screened from TCMSP. The target set of mGSLJZ for GC was obtained based on SwissTargetPrediction. The PPI network was constructed to screen out core targets. GO and KEGG enrichment analyses were conducted to identify BPs, CCs, MFs and pathways. The "active ingredient-core target-pathway" regulatory network was constructed to obtain core substances. Subsequently, Oncomine, Proteinatlas and molecular docking were performed to validate these findings. The cell experiments were conducted to confirm the anti-GC effects of mGLSJZ. Results and conclusion Forty-one potential active ingredients were filtered out from 120 chemical substances in mGSLJZ, including various organic acids and flavonoids. The top 10 key targets, 20 related pathways and 6 core medicinal substances were obtained based on network pharmacology analysis. Molecular docking results indicated that the core substances and key targets had good binding activities. The cell experiments validated that mGSLJZ and the core substances inhibited the proliferation in multiple GC cells and that mGLSJZ restrained the migration of GC. Meanwhile, the top 5 targets and top 2 pathways were verified. The rescue experiments demonstrated that mGSLJZ suppressed the proliferation and migration of GC through the PI3K/AKT/HIF-1 pathway.
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Affiliation(s)
- Wenjie Huang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Fang Wen
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuai Ruan
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Peixing Gu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Suping Gu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Siyuan Song
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiayu Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Ye Li
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiatong Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Peng Shu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
- Corresponding author. 155 Hanzhong Road, Nanjing, Jiangsu Province, 210000, China.
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Yang P, Liu P, Li J. The Regulatory Network of Gastric Cancer Pathogenesis and Its Potential Therapeutic Active Ingredients of Traditional Chinese Medicine Based on Bioinformatics, Molecular Docking, and Molecular Dynamics Simulation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:5005498. [PMID: 36471693 PMCID: PMC9719429 DOI: 10.1155/2022/5005498] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 10/17/2022] [Accepted: 11/11/2022] [Indexed: 06/16/2025]
Abstract
OBJECTIVE This study aims to investigate the functional gene network in gastric carcinogenesis by using bioinformatics; besides, the diagnostic utility of key genes and potential active ingredients of traditional Chinese medicine (TCM) for treatment in gastric cancer have been explored. METHODS The Cancer Genome Atlas and Gene Expression Omnibus databases have been applied to analyze the differentially expressed genes (DEGs) between gastric cancer and normal gastric tissues. Then, the DEGs underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the Metascape database. The STRING database and the Cytoscape software were utilized for the protein-protein interaction network of DEGs and hub genes screening. Furthermore, survival and expression analyses of hub genes were conducted using Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases. By using the Comparative Toxicogenomics Database, the hub genes interconnected with active ingredients of TCM were analyzed to provide potential information for the treatment of gastric cancer. After the molecular docking of the active ingredients of TCM to specific hub gene receptor proteins, the molecular dynamics simulation GROMACS was applied to validate the conformation of the strongest binding ability in the molecular docking. RESULTS A total of 291 significant DEGs were found, from which 12 hub genes were screened out. Among these hub genes, the expressions of five hub genes including COL1A1, COL5A2, MMP12, SERPINE1, and VCAN were significantly correlated with the overall survival. Furthermore, four potential therapeutic active ingredients of TCM were acquired, including quercetin, resveratrol, emodin, and schizandrin B. In addition, the molecular docking results exhibited that the active ingredients of TCM formed stable binding with the hub gene targets. SERPINE1 (3UT3)-Emodin and COL1A1 (7DV6)-Quercetin were subjected to molecular dynamics simulations as conformations of continuing research significance, and both were found to be stably bound as a result of the interaction of van der Waals potentials, electrostatic, and hydrogen bonding. CONCLUSION Our findings may provide novel insights and references for the screening of biomarkers, the prognostic evaluation, and the identification of potential active ingredients of TCM for gastric cancer treatment.
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Affiliation(s)
- Peng Yang
- Ganzhou People's Hospital/Ganzhou Hospital Affiliated to Nanfang Hospital, Southern Medical University, Ganzhou 341000, China
| | - Peng Liu
- Ganzhou People's Hospital/Ganzhou Hospital Affiliated to Nanfang Hospital, Southern Medical University, Ganzhou 341000, China
| | - Junmao Li
- The National Pharmaceutical Engineering Center for Solid Preparationin Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330006, China
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Hu Q, Li LL, Peng Z, Yi P. Expression of hepatocyte nuclear factor 4 alpha, wingless-related integration site, and β-catenin in clinical gastric cancer. World J Clin Cases 2022; 10:7242-7255. [PMID: 36157990 PMCID: PMC9353908 DOI: 10.12998/wjcc.v10.i21.7242] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/17/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is the second most common cause of cancer-related deaths worldwide. Hepatocyte nuclear factor 4 alpha (HNF4α) that belongs to the nuclear hormone receptor superfamily, is overexpressed in GC tissues, and might be involved in the development of GC by regulating its downstream wingless-related integration site (WNT)/β-catenin signaling.
AIM To clarify the expression of HNF4α/WNT5a/β-catenin signaling proteins in clinical GC tissues.
METHODS We immunohistochemically stained pathological blocks of GC and matched para-cancerous tissues. The intensity of HNF4α, WNT5a and β-catenin staining in the tumor cells was determined according to cell rates and staining intensity. The correlations between GC and HNF4α, WNT5a, and β-catenin expression using chi-square and paired chi-square tests. Relationships between double-positive HNF4α and WNT5a expression and types of gastric tumor tissues were assessed using regression analysis. Correlations between HNF4α and WNT5a expression at the RNA level in GC tissues found in the TCGA database were analyzed using Pearson correlation coefficients.
RESULTS We found more abundant HNF4α and WNT5a proteins in GC, especially in mucinous adenocarcinoma and mixed GC than in adjacent tissues (P < 0.001). Low and high levels of cytoplasmic β-catenin respectively expressed in GC and adjacent tissues (P < 0.001) were not significantly associated with pathological parameters.
CONCLUSION The expressions of HNF4α and WNT5a could serve as early diagnostic biomarkers for GC.
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Affiliation(s)
- Qian Hu
- Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ling-Li Li
- Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ze Peng
- Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ping Yi
- Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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12
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Song SJ, Liu X, Ji Q, Sun DZ, Xiu LJ, Xu JY, Yue XQ. Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression. JOURNAL OF INTEGRATIVE MEDICINE 2022; 20:355-364. [PMID: 35249836 DOI: 10.1016/j.joim.2022.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 10/30/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVES Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
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Affiliation(s)
- Shang-Jin Song
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China; Strategic Support Force Xingcheng Special Duty Sanatorium, Xingcheng 125100, Liaoning Province, China
| | - Xuan Liu
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Qing Ji
- Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Da-Zhi Sun
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Li-Juan Xiu
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Jing-Yu Xu
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Xiao-Qiang Yue
- Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
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Li L, Wu W, Yin M. Effect of Hematocrit Injury on the Survival Rate of Advanced Malignant Tumors and Its Clinical Significance. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4968754. [PMID: 35756408 PMCID: PMC9217579 DOI: 10.1155/2022/4968754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/12/2022] [Accepted: 05/28/2022] [Indexed: 01/28/2023]
Abstract
Objective To investigate the effect of logistic multivariate analysis on the survival rate of advanced malignant tumors and to evaluate the effect of erythrocyte storage injury on the survival rate of advanced malignant tumors and its clinical significance. Methods A retrospective analysis was performed on 120 advanced cancer patients who received blood transfusion in Shaanxi Cancer Hospital from March 2018 to June 2019, and the risk factors for death were analyzed. A total of 72 advanced cancer patients admitted to hospital from March 2019 to June 2021 were included in the study. The patients with red blood cell transfusion storage time ≤ 14 d were the study group (n = 36), and the patients with red blood cell transfusion storage time > 14 d were the control group (n = 36). Compare the total efficiency of blood transfusion. The levels of Hb, erythrocyte count, hematocrit (HCT), blood oxygen saturation (SPO2), creatinine (Cr), erythrocyte deformability index, whole blood, erythrocyte, and hemoglobin before and after blood transfusion were compared, and the adverse reactions of blood transfusion were recorded. Results Dyspnea and delirium were significantly associated with patient survival time (P < 0.05). Red blood cell storage time ≤ 14 days, Lym% < 12%, lactate dehydrogenase (LDH) > 500 U/L, and ALB < 30 g/L were significantly correlated with survival time. Karnofsky performance status (KPS) < 30, delirium, LDH > 500 U/L, and albumin (ALB) < 30 g/L were independent influencing factors of survival (P < 0.05). The overall effective rate of the research group was higher (P < 0.05). The incidence of adverse reactions in the study group was lower (P < 0.05). The levels of Hb, red blood cell count, and HCT in the study group were higher (P < 0.05). Compared with the control group, the SPO2 level and the red blood cell deformability index were higher in the study group (P < 0.05). After blood transfusion, the level of (diphosphoglycerate) DPG in the study group was higher than that in the control group (P < 0.05). The length of hospital stay in the study group was significantly shortened (P < 0.05). The nosocomial infection rate and case fatality rate in the study group were significantly reduced (P < 0.05). Conclusion Red blood cell storage time ≤ 14 d, LYM% < 12%, LDH > 500 U/L, and ALB < 30 g/L are all significantly correlated with survival time. KPS < 30, delirium, LDH > 500 U/L, and ALB < 30 g/L were independent factors for survival (P < 0.05). Transfusion of red blood cells stored for ≤14 days in patients with advanced malignant tumors can significantly increase the effective infusion rate, improve anemia status, shorten hospital stay, and reduce mortality and risk of nosocomial infection and is worthy of clinical promotion.
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Affiliation(s)
- Lin Li
- Shaanxi Provincial Cancer Hospital Pathology Department, 710068, China
| | - Weibin Wu
- Shaanxi Provincial Cancer Hospital Transfusion Department, 710068, China
| | - Mingdi Yin
- Shaanxi University of Chinese Medicine Faculty of Medicine and Technology Department of Laboratory, 710068, China
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Metal-organic framework-based hydrogel with structurally dynamic properties as a stimuli-responsive localized drug delivery system for cancer therapy. Acta Biomater 2022; 145:43-51. [PMID: 35398545 DOI: 10.1016/j.actbio.2022.04.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 03/18/2022] [Accepted: 04/01/2022] [Indexed: 12/13/2022]
Abstract
Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials, the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.e., self-healing and shear-thinning, as an injectable localized drug delivery platform. The drug-encapsulating MOF hydrogel is formed through a dynamic coordination bond cross-linkage between a doxorubicin-loaded MOF (MOF@DOX) particle and a homemade bisphosphonate-modified hyaluronic acid (HA-BP) polymeric binder. The HA-BP·MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and efficiently kills cancer cells in vitro. The animal experiments reveal that the HA-BP·MOF@DOX hydrogel has enhanced capability in terms of tumor growth suppression as compared to the MOF@DOX group, which can be attributed to drug localization in hydrogel superstructure and sustained release at the tumor site. The presented injectable dynamic MOF-based hydrogel is a promising in vivo localized drug delivery system for cancer treatment. Herein, we report the self-healing and shear-thinning of MOF-based drug carrier cross-linked by coordinate bonds for the first time and provide new insights and a facile chemical strategy for designing and fabricating MOF-based biomaterials by using bisphosphonate-zinc interaction. STATEMENT OF SIGNIFICANCE: Bisphosphonate-zinc interaction is a facile chemical strategy to cross-link metal-organic framework (MOF)-based hydrogel. The presented MOF-based hydrogel demonstrates structurally dynamic properties, including smooth injectability, self-healing, and shear-thinning. The developed MOF-based hydrogel possesses pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The dynamic MOF-based hydrogel shows enhanced in vivo anticancer activity as compared to pure MOF particles. Self-healing and shear-thinning of metal-ligand cross-linked MOF-based drug delivery system are reported for the first time, thus providing new insights for the design and fabrication of MOF-based biomaterials.
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15
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Wei L, Dong W, Han Z, Chen C, Jin Q, He J, Cai Y. Network Pharmacologic Analysis of Dendrobium officinale Extract Inhibiting the Proliferation of Gastric Cancer Cells. Front Pharmacol 2022; 13:832134. [PMID: 35401206 PMCID: PMC8989831 DOI: 10.3389/fphar.2022.832134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/17/2022] [Indexed: 12/26/2022] Open
Abstract
Globally, gastric cancer (GC) is one of the three most deadly cancers. Dendrobium officinale (D. officinale) is a traditional Chinese medicine (TCM), and its extract can significantly inhibit the proliferation of gastric cancer cells. However, there are no unified conclusions on its potential active components and possible mechanisms of action. This paper aims at exploring the potential active components, targets, and cell pathways of D. officinale extract in inhibiting the proliferation of gastric cancer cells by using network pharmacology and cytology experiments. In this paper, UPLC-MS/MS was used to identify the main chemical components in the extracts of D. officinale, and the an ADME model was used to screen the potential active components. Network pharmacology methods such as target prediction, pathway identification, and network construction were used to determine the mechanism through which the D. officinale extract inhibited gastric cancer cell proliferation. MTT assays, fluorescence confocal microscopy, clone formation, and flow cytometry were used to verify the inhibitory activity of the D. officinale extract on gastric cancer cell proliferation in vitro. The UPLC-MS/MS analysis identified 178 chemical components from the D. officinale extract. Network pharmacology analysis showed that 13 chemical components had the potential to inhibit the proliferation of gastric cancer cells, with the possible involvement of 119 targets and 20 potential signaling pathways. In vitro experiments confirmed that the D. officinale extract could significantly inhibit the proliferation of gastric cancer cells. Therefore, we believe that the D. officinale extract can inhibit the proliferation of gastric cancer cells through effects on multiple components, multiple targets, and multiple pathways.
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Affiliation(s)
- Lianping Wei
- School of Life Science, Anhui Agricultural University, Hefei, China
| | - Wenhao Dong
- School of Life Science, Anhui Agricultural University, Hefei, China
| | - Zhen Han
- Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China
| | - Chen Chen
- School of Life Science, Anhui Agricultural University, Hefei, China
| | - Qing Jin
- School of Life Science, Anhui Agricultural University, Hefei, China
| | - Jinling He
- School of Life Science, Anhui Agricultural University, Hefei, China
| | - Yongping Cai
- School of Life Science, Anhui Agricultural University, Hefei, China
- *Correspondence: Yongping Cai,
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16
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Zhang Y, Lin Y, Zhu Y, Zhang X, Tao L, Yang M. ARHGAP25 expression in colorectal cancer as a biomarker associated with favorable prognosis. Mol Clin Oncol 2022; 16:84. [PMID: 35251635 PMCID: PMC8892469 DOI: 10.3892/mco.2022.2517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/21/2022] [Indexed: 12/24/2022] Open
Abstract
Although progress has been made in the early diagnosis of colorectal cancer (CRC) and in the systemic therapy of patients with CRC, the prognosis for advanced CRC remains poor. Our previous study demonstrated that ARHGAP25 overexpression significantly inhibits CRC cell growth, invasion and migration. However, it was not possible to evaluate and analyze the overall survival (OS) rate of patients with CRC. Thus, the discovery of relevant factors and their expression on the basis of existing research is necessary to predict the OS rate of patients with advanced CRC. Therefore, the aim of the present study was to define the value of Rho GTPase-activating protein 25 (ARHGAP25) expression in predicting the OS rate in patients with CRC. The clinical data of 153 patients with CRC who underwent colorectal resection were retrospectively analyzed. In order to explore the expression of ARHGAP25, immunohistochemical analysis of the tumor tissues of these patients, was performed. Univariate Cox regression analysis was used to assess the prognostic value of ARHGAP25 expression for OS. Multivariate analysis was used to evaluate the effect of ARHGAP25 expression in the presence of other variables. Confounding factors and interaction were assessed by a stratified analysis using ARHGAP25 expression and other variables associated with survival. The univariate analysis revealed that, ARHGAP25 expression was associated with an improved OS in patients with CRC (P<0.05). The multivariate analysis revealed that ARHGAP25 expression was still correlated with an improved OS after adjusting for sex, age, invasion degree, lymph node metastasis, distant metastasis, TNM stage, tumor location, histological type, histological grade, tumor deposits, and postoperative treatment (P<0.05). The stratified analysis demonstrated that the predictive value of ARHGAP25 for the OS of patients with CRC was stronger in males, elderly patients (>70 years old), patients with T3 stage tumor, lymph node metastasis, TNM stage III, right hemicolon location and patients with a poorly differentiated tumor (P<0.05). Overall, our results demonstrated that ARHGAP25 may have an important potential value for improving the prognosis of patients with CRC.
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Affiliation(s)
- Yue Zhang
- Department of Oncology, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
| | - Yi Lin
- Department of Oncology, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
| | - Yingjie Zhu
- Department of Oncology, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
| | - Xiaoyun Zhang
- Department of Pathology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
| | - Li Tao
- Department of Oncology, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
| | - Ming Yang
- Phase I Clinical Research Laboratory of Shanghai LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China
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Guo SB, Huang WJ, Tian XP. Brusatol modulates diverse cancer hallmarks and signaling pathways as a potential cancer therapeutic. ACTA MATERIA MEDICA 2022; 1. [DOI: 10.15212/amm-2022-0014] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2024]
Abstract
Cancer is a consequence of uncontrolled cell proliferation that is associated with cell-cycle disruption. It is a multifactorial disease that depends on the modulation of numerous oncogenic signaling pathways and targets. Although a battle against cancer has been waged for centuries, this disease remains a major cause of death worldwide. Because of the development of resistance to current anticancer drugs, substantial effort has been focused on discovering more effective agents for tumor therapy. Natural products have powerful prospects as anticancer drugs. Brusatol, a component isolated from the plant Brucea javanica, has been demonstrated to efficiently combat a wide variety of tumors. Extensive studies have indicated that brusatol exhibits anticancer effects by arresting the cell cycle; promoting apoptosis; inducing autophagy; attenuating epithelial-mesenchymal transition; inhibiting migration, invasion and angiogenesis; and increasing chemosensitivity and radiosensitivity. These effects involve various oncogenic signaling pathways, including the MAPK, NF-κB, PI3K/AKT/mTOR, JAK/STAT and Keap1/Nrf2/ARE signaling pathways. This review describes the evidence suggesting that brusatol is a promising drug candidate for cancer therapeutics.
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Affiliation(s)
- Song-Bin Guo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Wei-Juan Huang
- Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, P.R. China
| | - Xiao-Peng Tian
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
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Hou C, Yang D, Zhang Y, Li Y, He Z, Dai X, Lu Q, Wang S, Zhang X, Liu Y. Effect of Fuzheng Qingdu Therapy for Metastatic Gastric Cancer is Associated With Improved Survival: A Multicenter Propensity-Matched Study. Integr Cancer Ther 2021; 20:15347354211058464. [PMID: 34781754 PMCID: PMC8600555 DOI: 10.1177/15347354211058464] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients. PATIENTS AND METHODS Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients. RESULTS The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ2 = 33.39 and P < .0001). The PFS of TCM users was also longer than that of non-TCM users (χ2 = 4.95 and P = 0.026). Notably, Chinese herbal decoction, Shenmai and compound Kushen injections were commonly used for FZQD therapy. CONCLUSION This propensity-matched study showed that FZQD therapy could improve the survival of metastatic GC patients.
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Affiliation(s)
- Chao Hou
- College of Medicine, Yangzhou University, Yangzhou, PR China.,The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, PR China
| | - Die Yang
- College of Medicine, Yangzhou University, Yangzhou, PR China
| | - Yusen Zhang
- College of Medicine, Yangzhou University, Yangzhou, PR China
| | - Yifei Li
- College of Medicine, Yangzhou University, Yangzhou, PR China
| | - Zhengfei He
- Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yangzhou, PR China
| | - Xiaojun Dai
- Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yangzhou, PR China
| | - Qingyun Lu
- Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yangzhou, PR China
| | - Shanshan Wang
- Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yangzhou, PR China
| | - Xiaochun Zhang
- Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yangzhou, PR China
| | - Yanqing Liu
- College of Medicine, Yangzhou University, Yangzhou, PR China.,The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, PR China
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Xu L, Liu C, Ye Z, Wu C, Ding Y, Huang J. Overexpressed LINC00467 promotes the viability and proliferation yet inhibits apoptosis of gastric cancer cells via raising ITGB3 level. Tissue Cell 2021; 73:101644. [PMID: 34555778 DOI: 10.1016/j.tice.2021.101644] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 08/24/2021] [Accepted: 09/04/2021] [Indexed: 12/21/2022]
Abstract
Long non-coding RNA (lncRNA) LINC00467 plays a proto-oncogenic role in non-small cell lung cancer. However, its effect and modulatory mechanism in gastric cancer (GC) are unknown. Thereby, we elucidated the mechanism of LINC00467 in GC. LINC00467 level in GC tissues was assessed by bioinformatic analysis, and clinicopathological parameters from GC patients were collected. The levels of LINC00467, integrin subunit beta 3 (ITGB3), proliferating cell nuclear antigen (PCNA), cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) in tissue samples or treated GC cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), or Western blot. The viability, proliferation and apoptosis of GC cells were detected by methyl thiazolyl tetrazolium assay, colony formation assay, and flow cytometry. Levels of LINC00467 and ITGB3 were up-regulated in GC, and highly expressed LINC00467 was positively associated with tumor size, differentiation, N stage, and T stage in GC patients. LINC00467 was enriched in cytoplasm of GC cells, and overexpressed LINC00467 promoted the viability and proliferation as well as levels of ITGB3 and PCNA, while suppressing the apoptosis and levels of cleaved caspase-3 and cleaved PARP1 in GC cells. Besides, the effects of shLINC00467 on inhibiting cell viability, proliferation of GC cells and PCNA level and promoting apoptosis as well as levels of cleaved caspase-3 and cleaved PARP1 were all partially reversed by overexpressed ITGB3. Overexpressed LINC00467 enhanced the viability and proliferation but inhibited apoptosis of GC cells via increasing ITGB3 level.
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Affiliation(s)
- Limao Xu
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Chengmin Liu
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Zhiyao Ye
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Chengfeng Wu
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Yuhang Ding
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China
| | - Juan Huang
- Gastroenterology Department, The 3(rd) Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China.
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20
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Pu H, Qian Q, Wang F, Gong M, Ge X. Schizandrin A induces the apoptosis and suppresses the proliferation, invasion and migration of gastric cancer cells by activating endoplasmic reticulum stress. Mol Med Rep 2021; 24:787. [PMID: 34498719 PMCID: PMC8441983 DOI: 10.3892/mmr.2021.12427] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 08/02/2021] [Indexed: 01/30/2023] Open
Abstract
Apart from its basic antioxidant and anti-inflammatory properties, schizandrin A (SchA), which is isolated from Fructus schisandra, can exert anticancer effects on multiple cancer types. However, to the best of our knowledge, there has been no study identifying the impacts of SchA on gastric cancer (GC). Therefore, the aim of the present study was to identify how SchA functioned to affect the progression of GC. To investigate the role of SchA in GC development, Cell Counting Kit-8, colony formation, wound healing and Transwell assays were conducted to assess the viability, proliferation, migration and invasion of AGS cells, respectively. Then, the apoptosis rate and apoptosis- and endoplasmic reticulum (ER) stress-related protein expression levels in AGS cells exposed to SchA were detected via TUNEL assays and western blotting, respectively. Subsequently, the aforementioned functional assays were performed again in AGS cells exposed to both SchA and the ER stress inhibitor 4-phenylbutyric acid (4-PBA) for the confirmation of the effect of SchA on ER stress in GC. It was found that SchA markedly decreased the viability, proliferation, migration and invasion, while it induced the apoptosis of AGS cells. Moreover, the markers of ER stress were elevated by SchA treatment in AGS cells. Nevertheless, 4-PBA reversed the effects of SchA on the viability, proliferation, migration, invasion and apoptosis of AGS cells, accompanied by decreased expression of ER stress markers. In conclusion, the present study demonstrated that SchA induced the apoptosis and suppressed the proliferation, invasion and migration of GC cells by activating ER stress, which provides a theoretical basis for the use of SchA in the treatment of GC.
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Affiliation(s)
- Huachao Pu
- Department of Oncology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, Jiangsu 213000, P.R. China
| | - Qian Qian
- Department of Gastroenterology, The First People's Hospital of Changzhou (The Third Affiliated Hospital of Soochow University), Changzhou, Jiangsu 213000, P.R. China
| | - Fuli Wang
- Department of Oncology, Changzhou Jin Dongfang Hospital, Changzhou, Jiangsu 213000, P.R. China
| | - Minjie Gong
- Department of Oncology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, Jiangsu 213000, P.R. China
| | - Xinguo Ge
- Department of Oncology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, Jiangsu 213000, P.R. China
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Exploring the Antitumor Mechanisms of Zingiberis Rhizoma Combined with Coptidis Rhizoma Using a Network Pharmacology Approach. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8887982. [PMID: 33426081 PMCID: PMC7781700 DOI: 10.1155/2020/8887982] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/30/2020] [Accepted: 11/25/2020] [Indexed: 12/24/2022]
Abstract
Background Although the combination of Zingiberis rhizoma (ZR) and Coptidis rhizoma (CR) is a classic traditional Chinese medicine-based herbal pair used for its antitumor effect, the material basis and underlying mechanisms are unclear. Here, a network pharmacology approach was used to elucidate the antitumor mechanisms of ZR-CR. Materials and Methods To predict the targets of ZR-CR in treating tumors, we constructed protein–protein interactions and hub component-target networks and performed pathway and process enrichment and molecular docking analysis. We used a surface plasmon resonance (SPR) assay to validate the predicted component-target affinities. Hub gene expression and survival analysis in patients with tumors were used to predict the clinical significance. Results The active components of ZR-CR—shogaol, daucosterol, ginkgetin, berberine, quercetin, chlorogenic acid, and vanillic acid—exhibited antitumor activities via the MAPK, PI3K-AKT, TNF, FOXO, HIF-1, and VEGF signaling pathways. Molecular docking and SPR analyses suggested direct binding of berberine with AKT1 and TP53; quercetin with EGFR and VEGF165; and ginkgetin, isoginkgetin, and daucosterol with VEGF165 with weak affinities. Gene expression levels of the hub targets of ZR-CR were associated with overall survival and disease-free survival in patients with various tumor types. Conclusions The antitumor components of the ZR-CR herbal pair and the mechanisms underlying their antitumor effects were identified. These antitumor components deserve to be explored further in experimental and clinical studies.
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Zhao S, Guan X, Hou R, Zhang X, Guo F, Zhang Z, Hua C. Vitexin attenuates epithelial ovarian cancer cell viability and motility in vitro and carcinogenesis in vivo via p38 and ERK1/2 pathways related VEGFA. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1139. [PMID: 33240988 PMCID: PMC7576048 DOI: 10.21037/atm-20-5586] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/28/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND Epithelial ovarian cancer (EOC) is the most common type of ovarian tumor, however, effective treatment does not currently exist for this condition. This study evaluated the role of vitexin in mitigating EOC both in vitro and in vivo. METHOD SKOV-3 cells were used for in vitro experimentation. Xenotransplantation mouse models were set up by subcutaneously injecting mice with SKOV-3 cells. CCK8 was used to screen the optimal dose in vitro. Cell proliferation, invasion, number of microtubule nodules and apoptosis were respectively detected by colony formation assay, transwell assay, microtubule formation assay and flow cytometry. TUNEL and immunohistochemistry were used to detect tissues apoptosis and VEGF content. Western blot assay was used to detect the expression of Ki67, caspase-3, VEGFA, VEGFR2, ERK1/2 and p38. RESULTS In vitro experiment, compared with the control group, 10 µL of vitexin significantly reduced Ki67 levels and enhanced tumor cell apoptosis rate. Additionally, the colony forming rate, invasive cells per field, and number of nodes/HPF in vitexin treated group decreased dramatically. The result of western blot showed that levels of p-p38/p38 and p-ERK1/2/ERK1/2 also noticeably decreased. In vivo experiment, 40 mg/kg of vitexin significantly inhibited tumor growth. In addition, vitexin significantly enhanced the percentage of tissues apoptosis, which was accompanied by a decrease in the percentage of VEGF-positive cells. CONCLUSIONS Vitexin decreased the proliferation and invasion of SKOV-3 cells and noticeably reduced tumor growth. These findings suggest that vitexin could be a promising therapy for EOC.
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Affiliation(s)
- Shuzhen Zhao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Xinlei Guan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Ruijie Hou
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Xueying Zhang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Fang Guo
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Zhifang Zhang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Caihong Hua
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
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Li P, Shi Y, Zhao B, Xu W, Xu Z, Zhang J, Guo Z, Bi Y, Wang T, Qin Y, Wang T. Pharmacological evaluation and mechanistic study of compound Xishu Granule in hepatocellular carcinoma. JOURNAL OF TRADITIONAL CHINESE MEDICAL SCIENCES 2020. [DOI: 10.1016/j.jtcms.2020.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Luan F, He X, Zeng N. Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems. J Pharm Pharmacol 2020; 72:1491-1512. [PMID: 32696989 DOI: 10.1111/jphp.13339] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 06/21/2020] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Tetrandrine, a natural bisbenzylisoquinoline alkaloid, possesses promising anticancer activities on diverse tumours. This review provides systematically organized information on cancers of tetrandrine in vivo and in vitro, discuss the related molecular mechanisms and put forward some new insights for the future investigations. KEY FINDINGS Anticancer activities of tetrandrine have been reported comprehensively, including lung cancer, colon cancer, bladder cancer, prostate cancer, ovarian cancer, gastric cancer, breast cancer, pancreatic cancer, cervical cancer and liver cancer. The potential molecular mechanisms corresponding to the anticancer activities of tetrandrine might be related to induce cancer cell apoptosis, autophagy and cell cycle arrest, inhibit cell proliferation, migration and invasion, ameliorate metastasis and suppress tumour cell growth. Pharmaceutical applications of tetrandrine combined with nanoparticle delivery system including liposomes, microspheres and nanoparticles with better therapeutic efficiency have been designed and applied encapsulate tetrandrine to enhance its stability and efficacy in cancer treatment. SUMMARY Tetrandrine was proven to have definite antitumour activities. However, the safety, bioavailability and pharmacokinetic parameter studies on tetrandrine are very limited in animal models, especially in clinical settings. Our present review on anticancer potentials of tetrandrine would be necessary and highly beneficial for providing guidelines and directions for further research of tetrandrine.
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Affiliation(s)
- Fei Luan
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xirui He
- Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Nan Zeng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Wang J, Dong Y, Li Q. Neferine induces mitochondrial dysfunction to exert anti-proliferative and anti-invasive activities on retinoblastoma. Exp Biol Med (Maywood) 2020; 245:1385-1394. [PMID: 32460625 DOI: 10.1177/1535370220928933] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in Nelumbo nucifera. This study evaluated the mitigation role of Neferine on retinoblastoma in vitro and in vivo. Xenotransplantation model was established by injecting WERI-Rb-1 cells subcutaneously. Upon induction of retinoblastoma , mice were intraperitoneally injected with Neferine (0, 0.5, 1, 2 mg/kg) or ethanol every 3 days for 30 days. Tumor weight and tumor volume were measured every three days and compared between four groups. Then, mice were sacrificed and immunohistochemical examination was performed to compare Ki67, VEGF content between groups. WERI-Rb-1 cells were used for in vitro experiments and the anti-angiogenic role of Neferine was assessed by analyzing nodes/HPF number. In WERI-Rb-1 xenotransplantation model, compared with control group, 1 mg/kg Neferine treatment significantly inhibited tumor weight (0.39 ± 0.04 g vs. 0.25 ± 0.03 g, P< 0.05) and tumor volume (2163 ± 165 mm3 vs. 1276 ± 108 mm3, P< 0.05) after 30 days. Compared with ethanol-injected mice, 2 μM Neferine treatment significantly enhanced apoptosis rate (2.1 ± 0.6% vs. 14.6 ± 2.6%, P< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%, P< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) expression. Additionally, 2 μM Neferine treatment significantly decreased JC-1 red/green percentage. High-dose Neferine could decrease retinoblastoma angiogenesis in association with a significant inhibition on tumor growth and invasion. These findings suggested that Neferine could be a new treatment or adjuvant against retinoblastoma.
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Affiliation(s)
- Jing Wang
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Yanmin Dong
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Qiuming Li
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
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Zhang F, Liu X, Huo B, Li B, Zhang R. Mechanism Analysis of Coix Seed in Gastric Cancer Treatment Based on Biological Network Modules. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20927521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Coix seed, the mature seed of Coix lacryma-jobi L., is a traditional herb widely used in various cancer adjuvant treatments; however, its mechanism is unknown. The aim of this study was to reveal the multitarget mechanisms of Coix seed in the treatment of gastric cancer (GC) by biological network and modular analysis methods. Forty-one ingredients and 482 targets of Coix seed and 165 GC-related genes were obtained from databases. Twelve on-target genes ( AICDA, CASP3, EP300, ERBB2, FGFR2, IL12A, IL12B, IL1B, LOX, TJP1, TP53, and TRIB3) of Coix seed overlapped with GC-related genes. Using compound-target and protein–protein interaction network analyses, we discovered the core targets of Coix seed. Markov cluster algorithm-based modular analysis identified 5 potential module targets of Coix seed for GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated the vast actions of Coix seed, which involve pathways in cancer, the cell cycle, receptor signal transduction, deoxyribonucleic acid damage response, transcriptional regulation, apoptosis, and cell connections. This study elucidated the potential mechanisms of Coix seed on GC, which may lead to the development of an effective drug. Additionally, this study showed the feasibility of network and modular analysis methods to investigate traditional Chinese medicinal herbal mechanisms and may provide a new angle for further research in the field of anticancer mechanisms and multitarget drugs.
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Affiliation(s)
- Fengbin Zhang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaoyan Liu
- Department of TCM Pediatric, TCM Hospital of Hebei Province, Shijiazhuang, China
| | - Bingjie Huo
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bing Li
- Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruixing Zhang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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ZiYinHuaTan Recipe Inhibits Cell Proliferation and Promotes Apoptosis in Gastric Cancer by Suppressing PI3K/AKT Pathway. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2018162. [PMID: 32382534 PMCID: PMC7193275 DOI: 10.1155/2020/2018162] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/15/2019] [Accepted: 07/25/2019] [Indexed: 01/26/2023]
Abstract
In recent years, traditional Chinese medicine has played an important role in the treatment of gastric cancer in China. ZiYinHuaTan (ZYHT) recipe was developed for advanced gastric cancer and had shown its promising value in the clinic. In this study, we explore the effect of ZYHT on gastric cancer in vitro and in vivo. ZYHT can inhibit tumor growth and improve the general condition of mice in subcutaneous transplantation nude mice models of gastric cancer. And ZYHT can also inhibit cell proliferation and blocked the cells in G0/G1 to induce cell apoptosis in HGC27 and MGC803 cells. Then, network pharmacology analysis showed that ZYHT may exert antitumor effect mainly through PI3K/AKT signaling pathway. Furthermore, the expression of PI3K, p-Akt, CyclinD1, and Bcl-2 was detected in vitro and in vivo. The results showed that ZYHT could decrease the expression of PI3K, CyclinD1, and Bcl-2 both in vitro and in vivo. These results suggested that ZYHT could be used as a method for the treatment of developed gastric cancer.
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Pan X, Tao H, Nie M, Liu Y, Huang P, Liu S, Sun W, Wu J, Ma T, Dai A, Lu J, Liu B, Zou X, Sun Q. A clinical study of traditional Chinese medicine prolonging the survival of advanced gastric cancer patients by regulating the immunosuppressive cell population: A study protocol for a multicenter, randomized controlled trail. Medicine (Baltimore) 2020; 99:e19757. [PMID: 32311976 PMCID: PMC7220101 DOI: 10.1097/md.0000000000019757] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 03/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a common high-mortality disease, causing a serious social burden. Traditional Chinese medicine has been utilized to prevent and treat GC for many years but its effects remain unclear. The aim of our study is to elucidate the anti-tumor effects and the possible mechanism of Jianpi Yangzheng Xiaozheng decoction. METHODS/DESIGN This is a prospective, multicenter, randomized controlled trial continuing 1.5 years. Two hundred ten eligible patients will be randomly divided into 2 groups, the chemotherapy alone and the chemotherapy combined with JPYZXZ group at a ratio of 1:2. All patients will receive the treatment for 24 weeks and follow up for 1.5 years. The primary outcomes are one-year survival rate, progression-free survival, and overall survival (OS), while the secondary outcomes are immune related hematology test, objective response rate, tumor makers, traditional Chinese medicine syndrome points, fatigue scale, and quality of life scale. All of these outcomes will be analyzed at the end of the trail. DISCUSSION This study will provide the objective evidence for the efficacy and safety of Jianpi Yangzheng Xiaozheng decoction in advanced GC. Furthermore, it will be helpful to form a therapeutic regimen in advanced GC by the combination of traditional medicine and western medicine.Trail registration: ChiCTR1900028147.
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Affiliation(s)
- Xiaoting Pan
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu
| | - Heyun Tao
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu
| | - Mengjun Nie
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu
| | - Yuanjie Liu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
- No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu
| | - Pan Huang
- Traditional Chinese Medicine Hospital of Zhangjiagang
| | - Shenlin Liu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | - Wei Sun
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | - Jian Wu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | | | - Anwei Dai
- Traditional Chinese Medicine Hospital of Kunshan
| | | | | | - Xi Zou
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | - Qingmin Sun
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
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Gao L, Hao CX, Zhang GL, Cao KX, Yu MW, Li QW, Ma XM, Yang GW, Wang XM. Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer. Chin J Integr Med 2020; 27:514-519. [PMID: 32144561 DOI: 10.1007/s11655-020-3191-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2020] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.
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Affiliation(s)
- Lei Gao
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Cai-Xia Hao
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Gan-Lin Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Ke-Xin Cao
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Ming-Wei Yu
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Qi-Wei Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xue-Man Ma
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Guo-Wang Yang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Xiao-Min Wang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
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Shu P, Tang H, Zhou B, Wang R, Xu Y, Shao J, Qi M, Xia Y, Huang W, Liu S. Effect of Yiqi Huayu Jiedu decoction on stages II and III gastric cancer: A multicenter, prospective, cohort study. Medicine (Baltimore) 2019; 98:e17875. [PMID: 31764782 PMCID: PMC6882584 DOI: 10.1097/md.0000000000017875] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 09/20/2019] [Accepted: 10/08/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND This study aimed to explore the effect of YHJD (Yiqi Huayu Jiedu decoction) in patients with stages II and III gastric cancer. METHODS A multicenter, prospective, cohort study was conducted in Jiangsu Province Hospital of Traditional Chinese Medicine, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital, People's Liberation Army Bayi Hospital, Changzhou Traditional Chinese Medicine Hospital, Changzhou Tumor Hospital, Traditional Chinese Medicine Hospital of Kunshan, Yangzhou Hospital of Traditional Chinese Medicine, and Yixing Tumor Hospital. A total of 489 patients with stage II or III gastric cancer were enrolled after radical gastrectomy. Among them, 238 were included in the chemotherapy group (received chemotherapy alone) and 251 in the YHJD group (received chemotherapy combined with YHJD). The DFS (disease-free survival) rate, 5-year survival rate, quality of life, and traditional Chinese medicine (TCM) symptoms of the 2 groups were compared. RESULTS The DFS curve of the YHJD group was higher than that of the chemotherapy group (P = .0042). The HR (hazard ratio) was 0.672, and its corresponding 95% CI (confidence interval) was 0.511 to 0.884. For stage II patients, the P value was .8323, which indicated that the difference was not significant. The risk HR was 0.938, and the corresponding 95% CI was 0.521 to 1.689. For stage III patients, the P value was .0072, indicating a statistically significant difference. The HR was 0.653, and the corresponding 95% CI was 0.477 to 0.893. The 5-year survival rate of the YHJD group was 85.29%, which was higher than that of the chemotherapy group (71.05%). Compared with the chemotherapy group, the YHJD group had better quality of life and lower TCM symptom scores. CONCLUSION YHJD decoction is effective in improving DFS rate in patients with gastric cancer stage III after radical gastrectomy. Moreover, it can reduce the risk of recurrence and metastasis and improve the quality of life in patients with gastric cancer stage II or III after radical gastrectomy.
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Affiliation(s)
- Peng Shu
- Oncology Department, Jiangsu Province Hospital of Traditional Chinese Medicine
| | - Huijuan Tang
- First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
- Department of Clinical and Molecular Sciences, Università Politenica delle Marche, Ancona, Italy
| | - Bin Zhou
- Oncology Department, Jiangsu Cancer Hospital
| | - Ruiping Wang
- Oncology Department, Jiangsu Province Hospital of Traditional Chinese Medicine
| | - Yuanyuan Xu
- Oncology Department, Jiangsu Province Hospital of Traditional Chinese Medicine
| | - Jie Shao
- Clinical Research Department, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu province, China
| | - Minghao Qi
- Clinical Research Department, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu province, China
| | - Yun Xia
- First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Wenjie Huang
- First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Shenlin Liu
- Oncology Department, Jiangsu Province Hospital of Traditional Chinese Medicine
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Wang B, Shen C, Li Y, Zhang T, Huang H, Ren J, Hu Z, Xu J, Xu B. Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling. Onco Targets Ther 2019; 12:5751-5765. [PMID: 31410021 PMCID: PMC6645696 DOI: 10.2147/ott.s208924] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 06/07/2019] [Indexed: 12/22/2022] Open
Abstract
Background: Chemotherapy remains a primary treatment method for advanced pancreatic cancer. However, chemotherapy resistance can influence the therapeutic effect of pancreatic cancer. The resistance mechanism of chemotherapeutic agents such as gemcitabine, which is an agent typically used to treat pancreatic cancer, is complicated and can be influenced by genes and the environment. Oridonin is a tetracyclic diterpenoid compound extracted from the traditional Chinese herb Rabdosia labtea. Oridonin may overcome drug resistance in pancreatic cancer, but researching pancreatic cancer drug resistance of chemotherapy by oridonin is not completely understood. Purpose: The present study aimed to assess the impact of oridonin on multidrug resistance proteins, apoptosis-associated proteins and energy metabolism in gemcitabine-resistant PANC-1 (PANC-1/Gem) pancreatic cancer cells. Methods: Gemcitabine resistance in PANC-1/Gem cells was induced using a concentration gradient of gemcitabine. Cell Counting Kit-8 assays were used to detect the impact of gemcitabine and oridonin on the proliferation of PANC-1 and PANC-1/Gem cells. Western blot analysis and immunofluorescence were used to detect the expression of multidrug resistance proteins, apoptosis-associated proteins and low-density lipoprotein receptor protein 1 (LRP1) proteins in PANC-1/Gem cells. The effects of gemcitabine and oridonin on PANC-1/Gem cells apoptosis were detected using flow cytometry. Animal xenograft tumor assays were used to detect the effect of gemcitabine and oridonin on pancreatic cancer in vivo. Furthermore, the ATP Assay kit was used to determine the effects of gemcitabine and oridonin on ATP levels in PANC-1/Gem cells. Immunofluorescence assays were used to detect the effects of gemcitabine and oridonin on the expression of low-density lipoprotein receptor protein 1 (LRP1) in PANC-1/Gem cells. In addition, LRP1 expression was knocked down in PANC-1/Gem cells via lentiviral vector-mediated RNA silencing. Clone formation assays and Western blot analysis were used to detect the effect of LRP1 knockdown on the proliferation of PANC-1/Gem cells. Results: The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance by regulating GST pi and LRP1/ERK/JNK signaling. Conclusion: In conclusion, the present study indicated that oridonin could overcome gemcitabine resistance in PANC-1/Gem cells by regulating GST pi and LRP1/ ERK/JNK signaling, inducing cell apoptosis. Therefore, oridonin with gemcitabine may be a promising preoperative treatment for patients who suffer from pancreatic cancer.
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Affiliation(s)
- Bili Wang
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Can Shen
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China.,Department of Clinical Laboratory, The Affiliated Yinzhou Hospital of Ningbo University, Ningbo 315040, People's Republic of China
| | - Yang Li
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Ting Zhang
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Hui Huang
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Jun Ren
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Zhengjun Hu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, People's Republic of China
| | - Jian Xu
- Department of Clinical Laboratory, Medical Technology College, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
| | - Bin Xu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China
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Pathological analysis of the superior mesenteric artery boundary in preoperative computed tomography of resectable pancreatic head adenocarcinoma. Oncol Lett 2019; 17:5711-5720. [PMID: 31186797 DOI: 10.3892/ol.2019.10269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Accepted: 03/26/2019] [Indexed: 11/09/2022] Open
Abstract
The aim of the present study was to evaluate the biological and prognostic implications of the superior mesenteric artery (SMA) boundary on preoperative abdominal contrast-enhanced computed tomography (CE-CT) for resectable adenocarcinoma of the pancreatic head. A total of 121 patients treated over a 6-year period at Peking University Third Hospital (Beijing, China) were included in the present study. The pattern of the SMA boundary was investigated on preoperative CE-CT and detailed pathological analysis of the extrapancreatic plexus [the pancreatic head plexus II (PLX-II) located on the right edge of the SMA] was performed. The results revealed that the radiological SMA boundary was associated with the grade of parasympathetic neurogenesis (P=0.014) in PLX-II, and was predictive of postoperative disease-free survival (P=0.014) and liver metastasis (P=0.013). Therefore, it was proposed that extrapancreatic parasympathetic neurogenesis may account for the different patterns of the SMA boundary on preoperative abdominal CE-CT, and affect the prognosis, particularly for liver metastasis in resectable pancreatic head adenocarcinoma.
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Huang Y, Zhu J, Lin X, Hong Y, Feng Y, Shen L. Potential of Fatty Oils from Traditional Chinese Medicine in Cancer Therapy: A Review for Phytochemical, Pharmacological and Clinical Studies. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2019; 47:727-750. [DOI: 10.1142/s0192415x19500381] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cancer management is a worldwide challenge. In addition to effective cancer therapies like chemotherapy, radiotherapy and surgery, treatment based on traditional Chinese medicine (TCM) and combined TCM with western medicine has gradually gained attention in Oriental countries. One potential TCM approach using extracted fatty oils, containing fatty acids which are important active ingredients with a variety of pharmacological activities, makes significant contributions to cancer treatment. The strategies of treating cancer with the fatty oils of TCM were classified into “Fuzheng”, which usually associates with improving immunity, represented by coix seed oil. The other classification is “Quxie”, which relates to inducing apoptosis of cancer cells, and is represented by Brucea javanica oil. Compared with other active substances, the literature about anticancer fatty oils is relatively limited, and most of them focus on the composition and other biological activities without a systematic review. Therefore, based on the theories of “Fuzheng” and “Quxie” in TCM, in this paper, the anticancer effects of fatty oils have been reviewed. The chemical composition, anticancer mechanism, listed drugs, studying dosage form and clinical application of fatty oils have also been discussed. In summary, since there are different types and abundance of fatty oils among botanicals, anticancer effects of fatty oils can be achieved through two TCM theory-based strategies. We hoped that this review paper can reveal the anticancer potential of fatty oils and provide a reference for future related studies.
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Affiliation(s)
- Yanleng Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
| | - Jiayi Zhu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
| | - Xiao Lin
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
| | - Yanlong Hong
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
| | - Yi Feng
- Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
| | - Lan Shen
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai-lun Road, Pudong District, Shanghai 201203, P. R. China
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Efficacy and Safety of Xiao Ai Ping Injection Combined with Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:3821053. [PMID: 31236124 PMCID: PMC6545757 DOI: 10.1155/2019/3821053] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 04/16/2019] [Indexed: 12/24/2022]
Abstract
Xiao Ai Ping injection (XAPI), extracted from the Chinese herbal medicine Marsdenia tenacissima, is widely used in the adjuvant treatment of tumors in China. The present study aimed to evaluate the efficacy and safety of XAPI combined with chemotherapy for treating patients with advanced gastric cancer. Seven databases were searched for relevant studies published up to October 1, 2018, and Review Manager 5.3 software and Stata 12.0 software were used for meta-analysis. Fourteen studies, representing 1097 enrolled patients, were included in our analysis. Compared with chemotherapy alone, combination treatment with XAPI and the XELOX regimen (capecitabine plus oxaliplatin) was found to improve the objective response rate (ORR) [RR=1.36; 95%CI (1.10, 1.70); P=0.006], disease control rate (DCR) [RR=1.15; 95% CI (1.04, 1.28); P=0.010], and Karnofsky Performance Status (KPS) improvement rate [RR=1.51; 95%CI (1.14, 2.00); P=0.004] and to reduce the incidence of leukopenia [RR=0.68; 95%CI (0.55,0.84); P=0.0005], liver damage [RR=0.59; 95% CI (0.37, 0.92); P=0.02], renal impairment [RR=0.39; 95% CI (0.18, 0.85); P=0.02], and hand-foot syndrome [RR=0.56; 95%CI (0.35,0.90); P=0.02]. However, median progression-free survival (PFS), 1-year survival rate, and median overall survival (OS) were not extended by XAPI plus XELOX. Combination treatment with XAPI and the SOX regimen (tegafur plus oxaliplatin) did not improve ORR or DCR, but it did enhance the KPS improvement rate [RR=1.73; 95%CI (1.23,2.43); P=0.002] and reduce the incidence of nausea and vomiting [RR=0.66; 95% CI (0.50, 0.88); P=0.004]. XAPI in combination with the FOLFOX regimen (fluorouracil/calcium folinate/oxaliplatin) enhanced only the KPS improvement rate [RR=1.68; 95%CI (1.18,2.39); P=0.004] and had no significant effect on ORR or DCR or the incidence of adverse events. A single study reported that XAPI combined with the CPT-11 regimen (irinotecan) was superior to chemotherapy alone with respect to DCR and also reduced the incidence of leukopenia, liver damage, and hand-foot syndrome during chemotherapy, while prolonging PFS. Finally, one study reported that XAPI combined with the TP regimen (palitaxel plus cisplatin) improved ORR and KPS improvement rate to a greater extent than TP alone. Although the present review has some limitations, the findings suggest that XAPI combined with chemotherapy may represent a beneficial treatment strategy, particularly the combination of XAPI and XELOX.
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Molecular targets of β-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review. Biomed Pharmacother 2019; 114:108812. [PMID: 30965237 DOI: 10.1016/j.biopha.2019.108812] [Citation(s) in RCA: 167] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 03/18/2019] [Accepted: 03/26/2019] [Indexed: 12/11/2022] Open
Abstract
β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of β-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of β-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. β-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, β-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies have shown that β-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, β-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied and identified.
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Bao WR, Li ZP, Zhang QW, Li LF, Liu HB, Ma DL, Leung CH, Lu AP, Bian ZX, Han QB. Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis. Front Pharmacol 2019; 9:1580. [PMID: 30804792 PMCID: PMC6378367 DOI: 10.3389/fphar.2018.01580] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 12/31/2018] [Indexed: 12/11/2022] Open
Abstract
Purpose: The purpose of this study was to determine if an Astragalus polysaccharide (RAP) can protect immune cells from the toxic side effects of paclitaxel (Taxol), a powerful anti-tumor drug whose equally powerful side effects limit its clinical use. Methods: We hypothesized that RAP can reduce the toxic effects induced by Taxol. To test this hypothesis, we conducted a series of studies in vivo and in vitro. First, we confirmed RAP's effects in vivo utilizing BALB/c mice inoculated with 4T1 mouse breast cancer cells as the tumor model. Mice were treated with RAP and/or Taxol, and the differences in the life spans were recorded. Second, a co-culture cell model was used to study the protective effect of RAP on cells vis-a-vis Taxol. The cell cycle and apoptosis of RAW 264.7 cells that were treated with RAP with/without Taxol were checked by flow cytometry and Hoechst staining. Proteins involved in the cell cycle and apoptosis were also tested by Western blot to reveal the probable mechanism. Results: RAP prolonged the life span of tumor-bearing mice treated with Taxol. The in vitro experiments showed that Taxol suppressed the proliferation of RAW 264.7 cells while RAP protected the RAW 264.7 cells from Taxol-induced suppression. The protection is selective because RAP had no effect on 4T1 cells. Furthermore, Taxol clearly led to cell cycle arrest mainly at the G2/M phase and generated cytotoxicity against RAW 264.7 cells, while RAP blocked cell cycle arrest and protected cells from apoptosis. Taxol up-regulated the protein levels of P-H2A, PARP, Chk1, p53, and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins. Conclusion: These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis.
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Affiliation(s)
- Wan-Rong Bao
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Zhi-Peng Li
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Quan-Wei Zhang
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Li-Feng Li
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Hong-Bing Liu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Dik-Lung Ma
- Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Chung-Hang Leung
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Ai-Ping Lu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Zhao-Xiang Bian
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Quan-Bin Han
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
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Yang L, Zhang S, Guo K, Huang H, Qi S, Yao J, Zhang Z. miR-125a restrains cell migration and invasion by targeting STAT3 in gastric cancer cells. Onco Targets Ther 2018; 12:205-215. [PMID: 30636883 PMCID: PMC6309784 DOI: 10.2147/ott.s168454] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Recently, many microRNAs have been found to be involved in the cancer progression including miR-125a. However, the underlying mechanisms of miR-125a in gastric cancer (GC) remain to be completely elucidated. OBJECTIVE The study was to investigate the functional role of miR-125a and the expression relevance of signal transducer and activator of transcription 3 (STAT3) and hyaluronan synthase 1 (HAS1). METHOD CCK-8 assay, scratch wound healing and transwell assay were conducted to identify the functional role of miR-125a in GC. In addition, using bioinformatics analysis, the target regulation relationship was found in STAT3 and miR-125a. To confirm the relationship, luciferase reporter assay was performed. More importantly, quantitative polymerase chain reaction and western blot assay were carried out to determine the association among miR-125a, STAT3 and HAS1 in GC cells. RESULTS Overexpressed miR-125a inhibited the migration and invasion of GC cells through scratch wound healing and transwell assay, and its knockdown displayed adverse effects, but the viability of GC cells did not show significant difference using CCK-8 assay. In addition, we identified that the knockdown of STAT3 or HAS1 remarkably suppressed the migration and invasion abilities of GC cells. Using bioinformatics analysis, miRTar, in particular, indicated that the 3'-untranslated region of STAT3 binds to miR-125a with a high score. Subsequently, we also verified that STAT3 was a target of miR-125a via luciferase reporter assay. Furthermore, we found that upregulated miR-125a expression could conspicuously constrain STAT3 expression at both protein and mRNA levels in MKN45 and NCI-N87 cells using quantitative polymerase chain reaction and Western blot assay, but no significant difference had been found in SGC 7901 cells. To further identify the regulatory relationship between miR-125a and STAT3, downregulation of miR-125a in MKN45 and NCI-N87 cells was carried out, which showed that the protein and mRNA expression levels of STAT3 were declined in two cell lines. Finally, we observed that upregulated miR-125a could lead to the decrease of HAS1 at protein and mRNA levels, whereas its knockdown revealed opposite effects. Meanwhile, we noticed that overexpression of STAT3 could induce the escalation of HAS1 at protein and mRNA expression levels and its knockdown exhibited the adverse outcomes. CONCLUSION These findings indicated that miR-125a may control the HAS1 expression in GC progression by targeting STAT3, which is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in GC.
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Affiliation(s)
- Liu Yang
- Department of Cancer Biotherapy Center, Hubei Cancer Hospital, Wuhan, Hubei 430079, China
| | - Shuguang Zhang
- Department of Clinical Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
| | - Kai Guo
- Department of Gastroenterology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Hu Huang
- Department of Oncology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Shuai Qi
- Department of Pharmacy, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Jie Yao
- Department of Urological Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China,
| | - Zhihong Zhang
- Department of Oncology, Gong'an County People's Hospital, Jingzhou, Hubei 434000, China,
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Liu X, Li M, Wang X, Dang Z, Jiang Y, Wang X, Yang Z. Effect of serum triglyceride level on the prognosis of patients with hepatocellular carcinoma in the absence of cirrhosis. Lipids Health Dis 2018; 17:248. [PMID: 30400953 PMCID: PMC6220457 DOI: 10.1186/s12944-018-0898-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 10/23/2018] [Indexed: 02/08/2023] Open
Abstract
Background The liver plays an important role in the metabolism of lipid and lipoprotein. Dyslipidemia has been demonstrated to be related with several cancers, but the association between serum lipid and hepatocellular carcinoma (HCC) in the absence of cirrhosis remains unclear. Methods A total of 2528 patients with HCC at the Beijing Ditan Hospital between February 2008 and December 2017 were retrospectively included in the study. We identified 200 patients with HCC without cirrhosis by histopathology, imaging, endoscopic findings, and laboratory tests. Multivariate regression analysis was performed to determine the independent characteristics associated with HCC without cirrhosis and its prognosis. Results In the logistics regression analysis, compared to patients with HCC with cirrhosis, patients with HCC without cirrhosis were more likely to have elevated triglyceride (TG) levels (OR = 2.66; 95% CI, 1.18–6.01; P = 0.019). The Kaplan-Meier analysis revealed that a lower TG level was a risk factor regardless of the presence of cirrhosis. The results of the Cox proportional hazard regression analysis showed that a decreased TG level was significantly related to a worse overall survival (HR = 0.51; 95% CI, 0.29–0.89; P = 0.017). Conclusion Serum TG level may be an independent factor to predict the prognosis of patients with HCC in the absence of cirrhosis. Electronic supplementary material The online version of this article (10.1186/s12944-018-0898-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiaoli Liu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Mengge Li
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Xinhui Wang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Zhibo Dang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Yuyong Jiang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Xianbo Wang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China
| | - Zhiyun Yang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.
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Qu G, Ma Z, Tong W, Yang J. LncRNA WWOX‑AS1 inhibits the proliferation, migration and invasion of osteosarcoma cells. Mol Med Rep 2018; 18:779-788. [PMID: 29845204 PMCID: PMC6059707 DOI: 10.3892/mmr.2018.9058] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 04/16/2018] [Indexed: 02/06/2023] Open
Abstract
Recently, numerous long non-coding (lnc)RNAs have been revealed as serving important roles in human gene regulation. Previous studies have suggested that aberrant expression of lncRNAs is associated with cancer progression and metastasis. Previous studies have also demonstrated that decreased expression of WW domain-containing oxidoreductase (WWOX) is associated with poor prognosis in numerous cancer types. However, the effect of WWOX antisense RNA 1 (WWOX-AS1) in the development of cancer remains unknown. The aim of the present study was to investigate the role of WWOX-AS1 in osteosarcoma. The expression levels of WWOX-AS1 in human osteosarcoma cell lines and a normal osteoblastic cell line were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results revealed that WWOX-AS1 expression was downregulated in osteosarcoma tissues. Furthermore, the association between WWOX-AS1 and the prognosis of patients with osteosarcoma was investigated using Kaplan-Meier and log-rank tests. The results suggested that patients exhibiting high WWOX-AS1 expression demonstrated a greater overall survival compared with patients exhibiting low WWOX-AS1 expression. In addition, overexpression and knockdown of WWOX-AS1 was performed using transfection experiments and confirmed by RT-qPCR in MG63 and SAOS2 cells, respectively. The results demonstrated that WWOX-AS1 and WWOX expression were positively correlated. Furthermore, the results of the knockdown and overexpression functional experiments suggested that WWOX-AS1 overexpression inhibited the proliferation, migration and invasion of MG63 cells, and knockdown of WWOX-AS1 enhanced the proliferation, migration and invasion of MG63 cells in SAOS2 cells. In conclusion, the results of the present study suggested that WWOX-AS1 may represent a potential biomarker and therapeutic target for the treatment of osteosarcoma.
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Affiliation(s)
- Gang Qu
- Department of Osteology, The 161th Hospital of People's Liberation Army, Wuhan, Hubei 430010, P.R. China
| | - Zhiqiang Ma
- Department of Osteology, The 161th Hospital of People's Liberation Army, Wuhan, Hubei 430010, P.R. China
| | - Wenxian Tong
- Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China
| | - Jiahui Yang
- Department of Osteology, The 161th Hospital of People's Liberation Army, Wuhan, Hubei 430010, P.R. China
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