EGFR干扰联合埃索美拉唑对胃癌AGS细胞增殖、凋亡、侵袭和自噬的影响

Effects of EGFR interference combined with Esomeprazole on proliferation,apoptosis,invasion and autophagy of gastric cancer AGS cells

目的 探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)干扰联合埃索美拉唑对胃癌细胞增殖、凋亡、侵袭和自噬的影响。方法 构建EGFR干扰和空载AGS细胞株,采用CCK-8法、EdU增殖实验、Transwell、流式细胞术分别检测细胞活力、增殖、侵袭、凋亡变化。细胞免疫荧光法检测细胞LC3、FOXO3a表达情况,Western blotting分析FOXO3a、EGFR、caspase3、PARP、SKP2蛋白表达。结果 与空载组细胞相比,EGFR干扰组细胞EGFR表达下调。埃索美拉唑处理显著抑制两组细胞活力、增殖、侵袭,诱导凋亡和自噬。埃索美拉唑处理后,与空载组相比,EGFR干扰组细胞活力降低,凋亡比例增加,Cleaved-caspase3上调,差异有统计学意义(P<0.05)。而两组细胞EdU阳性比例、侵袭细胞数量、LC3和FOXO3a荧光点数相比,差异均无统计学意义(P>0.05)。与空载组相比,EGFR干扰组细胞FOXO3a表达上调。结论 EGFR干扰联合埃索美拉唑可协同抑制胃癌细胞增殖和诱导凋亡,是一种潜在抗胃癌新策略,值得进一步研究。

Objective To investigate the effects of epidermal growth factor receptor(EGFR) interference combined with Esomeprazole on proliferation,apoptosis,invasion and autophagy of gastric cancer cells.Methods EGFR interference and empty vector transfected AGS cells were constructed.The cell viability,proliferation,invasion and apoptosis were detected by CCK-8,EdU proliferation assay,Transwell and flow cytometry,respectively.The expressions of LC3and FOXO3a were detected by immunofluorescence assay,and the expressions of FOXO3a,EGFR,caspase3,PARP and SKP2 proteins were analyzed by Western blotting.Results Compared with empty vector group,EGFR expression was down-regulated in EGFR interference group.Esomeprazole treatment significantly inhibited cell viability,proliferation,invasion,and induced apoptosis,autophagy in both groups(P0.05).FOXO3a expression was up-regulated in the EGFR interference group compared with the empty vector group(P<0.05).Conclusion EGFR interference combined with Esomeprazole can synergistically inhibit the proliferation and induce apoptosis of gastric cancer cells,which may be a potential new anti-gastric cancer strategy worthy of further investigation.