Gao H, Yin DF, Xing XR, Zhou LJ, Yu R. MiR-200a-3p/ZEB1/IRF1-mediated PANoptosis prompts Xiangshaliujunzi decoction to overcome 5-fluorouracil resistance in gastric cancer. World J Gastroenterol 2026; 32(14): 114331 [DOI: 10.3748/wjg.v32.i14.114331]
Corresponding Author of This Article
Rui Yu, Department of Technology, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan East Road, Huanggu District, Shenyang 110032, Liaoning Province, China. ruiyu690923@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/
World J Gastroenterol. Apr 14, 2026; 32(14): 114331 Published online Apr 14, 2026. doi: 10.3748/wjg.v32.i14.114331
MiR-200a-3p/ZEB1/IRF1-mediated PANoptosis prompts Xiangshaliujunzi decoction to overcome 5-fluorouracil resistance in gastric cancer
Hong Gao, Dong-Feng Yin, Xiang-Rong Xing, Li-Jiang Zhou, Rui Yu
Hong Gao, Dong-Feng Yin, Xiang-Rong Xing, Li-Jiang Zhou, Department of Oncology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
Rui Yu, Department of Technology, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
Author contributions: Gao H contributed to study design, data analysis, drafting the manuscript and revision of the manuscript; Yin DF, Xing XR, Zhou LJ contributed to data collection and analysis, drafting the manuscript, investigation; Yu R contributed to study design, methodology, review and editing the manuscript; and all authors read and approved the final version of the manuscript.
Supported by the Liaoning University of Traditional Chinese Medicine, No. YXIL-2024-1700-0524.
Institutional animal care and use committee statement: The procedures for care and use of animals were approved by the Ethics Committee of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and all applicable institutional and governmental regulations concerning the ethical use of animals were followed.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: All data generated or analyzed during this study are included in this published article.
Corresponding author: Rui Yu, Department of Technology, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan East Road, Huanggu District, Shenyang 110032, Liaoning Province, China. ruiyu690923@163.com
Received: September 28, 2025 Revised: November 14, 2025 Accepted: January 29, 2026 Published online: April 14, 2026 Processing time: 186 Days and 18.6 Hours
Abstract
BACKGROUND
One of the main challenges in treating gastric cancer is chemoresistance, particularly when using 5-fluorouracil (5-FU). Traditional Chinese medicine Xiangshaliujunzi decoction (XSLJZD) has been widely used for managing chemotherapy-related side effects; however, its potential antitumor effects remain unexplored. We aimed to study the role of XSLJZD in addressing 5-FU resistance in gastric cancer cells.
AIM
To investigate whether XSLJZD overcomes 5-FU resistance in gastric cancer by regulating miR-200a-3p/ZEB1/IRF1-mediated PANoptosis.
METHODS
BGC-823/5-FU cell line was constructed. ZEB1 and IRF1 knockdown cell lines were constructed by transfecting lentivirus vectors containing shRNAs targeting ZEB1 and IRF1. Cell viability and proliferation were detected by CCK8 and colony formation assays. Cell apoptosis was determined by flow cytometry. Cell necroptosis and pyroptosis were measured using fluorescence staining. The molecular mechanism of XSLJZD was further explored using western blot, RNA immunoprecipitation, co-immunoprecipitation, and dual-luciferase reporter assays. A xenograft tumor nude mouse model was constructed by subcutaneously injecting the gastric cancer cells.
RESULTS
XSLJZD significantly inhibited cell viability and proliferation while promoting PANoptosis in BGC-823/5-FU cells (5-FU-resistant cells). ZEB1 knockdown upregulated pyroptosis-, apoptosis-, and other programmed cell death (PCD)-related proteins. Simultaneous knockdown of ZEB1 and IRF1 suppressed the expression of pyroptosis-, apoptosis- and PCD-related proteins. The combination of XSLJZD and 5-FU promoted miR-200a/ZEB1/IRF1-mediated PANoptosis in transplanted tumor tissues from mice.
CONCLUSION
Our findings suggest that XSLJZD sensitizes gastric cancer cells to 5-FU by modulating the miR-200a-3p/ZEB1/IRF1 pathway, offering a potential therapeutic strategy to overcome chemoresistance.
Core Tip: Xiangshaliujunzi decoction (XSLJZD) overcomes 5-fluorouracil (5-FU) resistance in gastric cancer by inducing PANoptosis via the miR-200a-3p/ZEB1/IRF1 pathway. In vitro, XSLJZD inhibits viability and promotes cell death. In vivo, combination with 5-FU enhances this effect. This provides a novel traditional Chinese medicine strategy for chemoresistance, though limitations include lack of standalone controls and generalizability validation.
