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World J Gastroenterol. Jul 21, 2026; 32(27): 119490
Published online Jul 21, 2026. doi: 10.3748/wjg.119490
Hua-Zhuo-Jie-Du formula alleviates colitis-associated colorectal cancer via regulating phosphatidylinositol 3-kinase/protein kinase B signaling pathway
Shao-Pu Hu, Yan-Ru Cai, Yang Liu, Yu-Xi Guo, Xue-Mei Jia, Jian-Ming Jiang, Qian Yang
Shao-Pu Hu, Yan-Ru Cai, Yang Liu, Yu-Xi Guo, Xue-Mei Jia, Qian Yang, Department of Gastrointestinal Disease, The First Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang 050011, Hebei Province, China
Shao-Pu Hu, Yan-Ru Cai, Yang Liu, Yu-Xi Guo, Xue-Mei Jia, Jian-Ming Jiang, Qian Yang, Hebei Key Laboratory of Turbidity Toxin Syndrome, Hebei University of Chinese Medicine, Shijiazhuang 050011, Hebei Province, China
Shao-Pu Hu, Yan-Ru Cai, Yang Liu, Yu-Xi Guo, Xue-Mei Jia, Jian-Ming Jiang, Qian Yang, Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, Shijiazhuang 050011, Hebei Province, China
Jian-Ming Jiang, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China
Co-first authors: Shao-Pu Hu and Yan-Ru Cai.
Co-corresponding authors: Jian-Ming Jiang and Qian Yang.
Author contributions: Hu SP and Cai YR performed the experiments and wrote the manuscript; Liu Y conducted the network pharmacology analysis; Guo YX and Jia XM analyzed the data; Jiang JM and Yang Q designed the study and revised the manuscript; Hu SP and Cai YR contributed equally to this study, and are the co-first authors of this manuscript; Jiang JM and Yang Q contributed equally to this article, and are the co-corresponding authors of this manuscript; all authors have read and approved the final manuscript.
AI contribution statement: DeepSeek was used for language polishing and sentence optimization. All data analysis and scientific reasoning were performed by the authors.
Supported by the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine, No. 2025213; Hebei Natural Science Foundation, No. H2024423041, No. H2023423001 and No. H2024423025; and Merit-based Funding Project for Hebei Postdoctoral Researchers’ Scientific Research, No. B2024005036.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Committee for Ethics of Animal Experimentation at Hebei Provincial Hospital of Traditional Chinese Medicine (approval No. IACUC-HPHCM-2024016 and No. IACUC-HPHCM-2024058).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Study data can be obtained by contacting the corresponding author with appropriate justification.
Corresponding author: Qian Yang, MD, Professor, Department of Gastrointestinal Disease, The First Affiliated Hospital, Hebei University of Chinese Medicine, No. 389 Zhongshan East Road, Changan District, Shijiazhuang 050011, Hebei Province, China.
yangqian6909@163.com
Received: January 29, 2026
Revised: February 12, 2026
Accepted: March 13, 2026
Published online: July 21, 2026
Processing time: 159 Days and 21.2 Hours
BACKGROUND
Colitis-associated colorectal cancer (CAC) is a common type of malignant tumor that occurs in the digestive tract and poses a significant threat to human health. The traditional Chinese medicine preparation Hua-Zhuo-Jie-Du formula (HZJDF) has shown clinical efficacy in preventing CAC; however, the potential therapeutic mechanisms of this formula for treating CAC remain under explored.
AIM
To investigate the therapeutic efficacy and mechanism of HZJDF against CAC through applying an integrated research approach.
METHODS
We first established a CAC mouse model using the azoxymethane/dextran sulfate sodium induction method and then assessed the therapeutic effects of various doses of HZJDF on the CAC mice. Subsequently, we utilized a combination of network pharmacology and transcriptomics analyses to help predict the potential mechanisms by which HZJDF acts against CAC. Finally, we sought to validate these prediction findings through animal and cell experiments.
RESULTS
HZJDF significantly mitigated weight reduction and colon length shortening in a dose-dependent manner, enhanced the mice survival rates, lowered the disease activity index scores, diminished the tumor incidence and burden, and improved the pathological condition of the colon tissues in the CAC mice. The findings from the network pharmacology and transcriptomics analyses suggested that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway might be the potential mechanism through which HZJDF exerts its protective effects against CAC. In vivo studies showed that HZJDF diminished the quantity of Ki67-positive cells within the colon tissues of the CAC mice and lowered the levels of phosphorylated PI3K and AKT proteins. Meanwhile, in vitro studies indicated that serum containing HZJDF decreased the viability, proliferation, and migration of HT-29 and HCT116 cells in a dose-dependent manner, while also lowering the expression of key proteins linked to the PI3K/AKT signaling pathway.
CONCLUSION
HZJDF effectively alleviated CAC tumorigenesis by suppressing the PI3K/AKT signaling pathway, providing reliable evidence to support the appropriate utilization of HZJDF in CAC treatment.
Core Tip: Hua-Zhuo-Jie-Du formula (HZJDF) has been clinically proven to be effective at preventing colitis-associated colorectal cancer (CAC), but the mechanism for this requires further investigation. This study utilized ultra-high performance liquid chromatography-high-resolution mass spectrometry analysis, network pharmacology, and transcriptomics in an integrated approach to predict the material basis and potential mechanism of action of HZJDF in treating CAC. Furthermore, the prediction results were verified through animal and cell experiments. The results indicated that HZJDF effectively alleviated the tumorigenesis of CAC via inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.
