中国实验动物学报2026，Vol.34Issue(4)：469-482,14.DOI:10.3969/j.issn.1005-4847.2026.04.001
藤黄酸通过调控LRRC8A表达对胰腺癌化疗敏感性的影响
Effect of gambogic acid on chemosensitivity in pancreatic cancer through regulating LRRC8A expression
摘要
Abstract
Objective This study aimed to examine how gambogic acid(GA)modulates pancreatic cancer cell sensitivity to gemcitabine(GEM)chemotherapy,and to elucidate the underlying molecular mechanisms involved.Methods GEM-resistant pancreatic cancer cell lines were established using a concentration-escalation method,and GA suppressive activity against drug-resistant cell proliferation was assessed.The influence of GA on leucine-rich repeat-containing protein 8A(LRRC8A)expression was examined with quantitative reverse transcription PCR(RT-qPCR)and Western Blot analyses.A LRRC8A-knockdown patient-derived organoids(PDOs)model was constructed,and the half-maximal inhibitory concentration of GEM post-knockdown was measured using the Cell Titer-Glo luminescence assay to explore the synergistic effect of GA and GEM on cell viability.Potential targets through which GA mitigates chemoresistance were forecasted using network-based pharmacological approaches and molecular docking simulations,with subsequent Western Blot analyses providing experimental verification.Murine xenograft models bearing human pancreatic carcinoma were established to monitor the therapeutic impact of GA on neoplastic growth.Comparative immunohistochemical analysis of LRRC8A expression levels was conducted pre-and post-intervention.Results GA significantly inhibited the growth of GEM-resistant pancreatic cancer cells and patient-derived organoids and effectively enhanced cellular sensitivity to GEM by regulating LRRC8A/STAT3 signaling.In vivo experiments further confirmed that GA intervention significantly reduced LRRC8A expression and suppressed pancreatic cancer progression.Conclusions GA-mediated downregulation of LRRC8A conferred GEM sensitivity in pancreatic cancer cells.关键词
胰腺癌/藤黄酸/吉西他滨/耐药/富含亮氨酸重复序列蛋白8AKey words
pancreatic cancer/gambogic acid/gemcitabine/drug resistance/leucine-rich repeat-containing protein 8A分类
生物科学引用本文复制引用
李梦瑶,黄敏丽,张永斌,师长宏..藤黄酸通过调控LRRC8A表达对胰腺癌化疗敏感性的影响[J].中国实验动物学报,2026,34(4):469-482,14.基金项目
国家自然科学基金(32270566),陕西省创新能力支撑计划(2025JC-GXPT-043).Funded by the National Natural Science Foundation of China(32270566),Shaanxi Province Innovation Capability Support Plan(2025JC-GXPT-043). （32270566）
