摘要
目的:探讨埃索美拉唑联合表皮生长因子受体(EGFR)抑制剂AG1478对胃癌细胞增殖、迁移、凋亡、自噬的影响与分子机制.方法:实验分为空白对照组、埃索美拉唑组、AG1478组和埃索美拉唑联合AG1478组,采用CCK-8法、EdU增殖实验、Transwell、划痕实验、流式细胞术、细胞免疫荧光法分别检测各组人胃癌AGS、SGC-7901细胞活力、增殖、迁移、凋亡和自噬变化.Western blotting检测EGFR、c-MYC、P53、cleaved-PARP、LC3B、PI3K、AKT、P-AKT蛋白的表达情况.结果:AG1478 抑制胃癌细胞活力和EGFR表达呈浓度依赖性.埃索美拉唑和AG1478能够明显降低胃癌细胞活力、抑制其增殖和迁移,诱导细胞凋亡和自噬(P＜0.05),且两者联合有协同作用(P＜0.05).埃索美拉唑和AG1478 均能降低AGS和SGC-7901细胞PI3K、AKT、P-AKT蛋白的表达(P＜0.05),两者联合对降低P-AKT的表达有协同作用(P＜0.05).结论:埃索美拉唑联合EGFR抑制剂AG1478对胃癌细胞增殖、迁移有抑制作用,且二者协同诱导细胞凋亡和自噬,两者联合可能是一种潜在的个体化治疗策略.
Abstract
Objective:To investigate the effects and molecular mechanisms of esomeprazole combined with epidermal growth factor receptor(EGFR)inhibitor AG1478 on proliferation,migration,apoptosis and autophagy of gastric cancer cells.Methods:The experiment was divided into blank control group,esomeprazole group,AG1478 group and esomeprazole combined with AG1478 group.The viability,proliferation,migration,apoptosis and autophagy changes of human gastric cancer AGS and SGC-7901 cells in each group were detected by CCK-8 method,EdU proliferation assay,Transwell,flow cytometry and cell im-munofluorescence respectively.Western blotting was performed to detect the expression of EGFR,c-MYC,P53,cleaved-PARP,LC3B,PI3K,AKT,P-AKT proteins.Results:AG1478 inhibited the viability and EGFR expression of gastric cancer cells in a concentration-dependent manner.Esomeprazole and AG1478 significantly reduced gastric cancer cell viability,in-hibited their proliferation and migration,and induced apoptosis and autophagy(P＜0.05),and the combination of the two had a synergistic effect(P＜0.05).Esomeprazole and AG1478 both reduced the expression of PI3K,AKT and P-AKT proteins in AGS and SGC-7901 cells(P＜0.05),and the combination of the two had a synergistic effect on reducing the expression of P-AKT(P＜0.05).Conclusion:Esomeprazole combined with the EGFR inhibitor AG1478 has inhibitory effects on the proliferation and migra-tion of gastric cancer cells,and they synergistically induce apoptosis and autophagy,the combination of which may be a potential individualized treatment strategy.
基金项目
河南省科技攻关项目(212102310618)
河南省高等学校重点科研项目计划(22A320005)
河南省高等学校重点科研项目计划(21A320046)
河南省医学科技攻关计划项目(LHGJ20210488)
维普
万方数据