埃克替尼提高胃癌细胞对肿瘤坏死因子相关凋亡诱导配体的敏感性

摘要

Objective:Most gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).Our aim is to identify the reason of TRAIL resistance and how to enhance TRAIL sensitivity in gastric cancer cells.Methods:Cell apoptosis was determined by flow cytometry.Protein expression was detected by Western blot.Results:Treatment with TRAIL (100 ng/ml) for 20 h only triggered a little cell apoptosis in MGC803 and SGC7901 cells.Meanwhile,the activation of EGFR and downstream Akt,ERK was detected.Pretreatment with a novel EGFR tyrosine kinase inhibitor icotinib (10μmol/L) for 2h followed by TRAIL,the phosphorylation of EGFR and downstream Akt,ERK induced by TRAIL was inhibited,and icotinib finally increased TRAIL sensitivity in MGC803 and SGC7901 cells.Conclusion:Icotinib enhanced TRAIL-induced apoptosis in gastric cancer cells by the inhibition of EGFR pathway.%目的:胃癌细胞大多对TRAIL(tumor necrosis factor-related apoptosis-inducing ligand)不敏感.本研究为探讨胃癌细胞对TRAIL耐药的原因以及如何提高胃癌细胞对TRAIL的敏感性.方法:流式细胞术检测细胞凋亡,免疫印迹法检测蛋白的表达.结果:TRAIL(100ng/ml)作用MGC803和SGC7901细胞20小时,TRAIL诱导少量细胞凋亡,同时检测到EGFR和下游Akt、ERK的活化.用新型的EGFR酪氨酸激酶抑制剂埃克替尼(10μmol/L)预处理MGC803和SGC7901细胞2小时,之后加用TRAIL,结果抑制了TRAIL引起的EGFR和下游Akt、ERK的磷酸化,并最终提高了MGC803和SGC7901细胞对TRAIL的敏感性.结论:埃克替尼通过抑制EGFR通路从而增强了TRAIL诱导的胃癌细胞凋亡.