©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2026; 32(8): 113299
Published online Feb 28, 2026. doi: 10.3748/wjg.v32.i8.113299
Published online Feb 28, 2026. doi: 10.3748/wjg.v32.i8.113299
Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance
Si-Chan Li, Yu-Hang Zhang, Yu Zhou, Wen-Tao Shang, Qing-Long Guo, Xiao-Bo Zhang, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China
Shun-Zi Shao, Qi-Bin He, Department of Gastroenterology, Jiangning Hospital, Nanjing Medical University, Nanjing 211199, Jiangsu Province, China
Yuan Gao, Pharmaceutical Animal Experimental Center, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
Chuan-Yong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Nanjing Medical University, Shanghai 200072, China
Co-first authors: Si-Chan Li and Shun-Zi Shao.
Co-corresponding authors: Chuan-Yong Guo and Xiao-Bo Zhang.
Author contributions: Guo CY, Guo QL, Zhang XB contributed to conceptualization and funding acquisition; Zhou Y, Shang WT contributed to validation; Li SC, Shao SZ, Zhang YH contributed to formal analysis; Li SC, Shao SZ, Zhou Y contributed to investigation and visualization; He QB, Guo QL contributed to resources; Gao Y contributed to data curation; Li SC contributed to writing original draft; Guo CY, Zhang XB contributed to writing review and editing, and supervision; all authors have read and approved the final version to be published.
Supported by the “Double First-Class University” Project of China Pharmaceutical University, No. CPU2022PZQ11; Nanjing Medical Science and Technology Development Foundation, No. YKK24223; and Outstanding Young Teacher of Qinglan Project in Jiangsu Province.
Institutional review board statement: The patient-derived organoid study was approved by the Ethics Committee of Nanjing Jiangning Hospital (No. 2024-03-150-K01).
Institutional animal care and use committee statement: All animal experiments were approved by the Animal Ethics Committee of China Pharmaceutical University (No. 2024-08-093).
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: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Xiao-Bo Zhang, PhD, Doctor, Jiangsu Key Laboratory of Carcinoge
Received: August 21, 2025
Revised: September 17, 2025
Accepted: December 23, 2025
Published online: February 28, 2026
Processing time: 174 Days and 16.1 Hours
Revised: September 17, 2025
Accepted: December 23, 2025
Published online: February 28, 2026
Processing time: 174 Days and 16.1 Hours
Core Tip
Core Tip: We identified lysosomal trapping as a key mechanism of bortezomib resistance (BTZ) in gastric cancer. The novel agent V8 disrupts lysosomes, releasing BTZ to enhance proteasome targeting and induce lethal proteotoxic stress. The V8-BTZ combination shows strong synergy in cells, xenografts, and patient organoids, supporting its clinical potential for overcoming resistance.