Dai Y, Liu YY, Cao N, Tian XW, Feng J, Hu ZZ, Xu JQ. Overcoming chemoresistance in non-small cell lung cancer: Insights into the influence of inflammatory factors on treatment response. World J Clin Oncol 2025; 16(10): 112097 [DOI: 10.5306/wjco.v16.i10.112097]
Corresponding Author of This Article
Jian-Qiang Xu, MD, Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, No. 60 Qiao Hu Road, Xiling District, Yichang 443002, China. xjqdll930@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Oct 24, 2025 (publication date) through Oct 27, 2025
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Journal Information of This Article
Publication Name
World Journal of Clinical Oncology
ISSN
2218-4333
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Dai Y, Liu YY, Cao N, Tian XW, Feng J, Hu ZZ, Xu JQ. Overcoming chemoresistance in non-small cell lung cancer: Insights into the influence of inflammatory factors on treatment response. World J Clin Oncol 2025; 16(10): 112097 [DOI: 10.5306/wjco.v16.i10.112097]
Yue Dai, Nian Cao, Xiu-Wen Tian, Juan Feng, Zhen-Zhen Hu, Jian-Qiang Xu, Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang 443002, Hubei Province, China
Ya-Yun Liu, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, Hubei Province, China
Co-corresponding authors: Ya-Yun Liu and Jian-Qiang Xu.
Author contributions: Xu JQ and Liu YY contribute equally to this study as co-corresponding authors; Xu JQ, Liu YY and Dai Y conceptualized and designed the study, drafted the initial manuscript; Cao N, Tian XW, Feng Jand Hu ZZ collected the data and carried out the initial analyses; Xu JQ, Liu YY and Dai Y critically reviewed the manuscript for important intellectual content; all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Institutional review board statement: This study was approved by the Ethics Committee of Gezhouba Central Hospital of Sinopharm and conducted in accordance with the approval guidelines. All patients voluntarily signed the informed consent form. The study was conducted in accordance with the Declaration of Helsinki.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian-Qiang Xu, MD, Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, No. 60 Qiao Hu Road, Xiling District, Yichang 443002, China. xjqdll930@163.com
Received: July 18, 2025 Revised: July 31, 2025 Accepted: September 2, 2025 Published online: October 24, 2025 Processing time: 99 Days and 3.6 Hours
Abstract
BACKGROUND
Non-small cell lung cancer (NSCLC) is frequently characterized by poor response to cisplatin (DDP)-based chemotherapy, with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironment contribute to chemoresistance.
AIM
To investigate the role of inflammatory cytokines in DDP resistance and to effect of IL-6 inhibition on chemosensitivity in NSCLC.
METHODS
Twenty NSCLC patients were grouped into DDP-sensitive or DDP-resistant cohorts based on their clinical response. Cytokine levels in tumor tissues and NSCLC cell lines, including DDP-resistant A549/DDP and SK-MES-1/DDP, were quantified using enzyme-linked immunosorbent assay. To verify the effects of interleukin (IL)-6 on DDP resistance, NSCLC and resistant cells were treated with IL-6 inhibitors tocilizumab (TCZ), followed by DDP treatment. Cell viability, apoptosis, migration and invasion were detected via cell counting kit-8, flow cytometry, scratch assay, and transwell, respectively.
RESULTS
IL-6, IL-8, and tumor necrosis factor-α levels were significantly elevated in DDP-resistance tissues and cell models compared to sensitive controls (P < 0.05). TCZ treatment significantly reduced the half-maximal inhibitory concentration of DDP in resistant cells, induced apoptosis, and hindered migration and invasion (P < 0.05). IL-6 and IL-8 were identified as key cytokines associated with DDP resistance.
CONCLUSION
These findings demonstrated that IL-6 and related cytokines contribute to DDP resistance in NSCLC. IL-6 inhibition restores chemosensitivity and may serve as a promising therapeutic strategy in resistant NSCLC.
Core Tip: This study explores the association between inflammatory cytokines and cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). Elevated levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α were detected in DDP-resistant tissues and cells. Notably, inhibition of IL-6 using the receptor antagonist tocilizumab restored DDP sensitivity by reducing cell viability, migration, and invasion, while enhancing apoptosis. These findings underscore IL-6 as a promising therapeutic target to overcome DDP resistance in NSCLC.
