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

Icotinib increases the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand

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。

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.