RG-14260与雷帕霉素联合给药对两株子宫内膜癌细胞的作用

目的观察体外EGFR信号通路抑制剂RG-14260单独及RG-14260联合mTOR信号通路抑制剂雷帕霉素对两株子宫内膜癌细胞(PTEN缺失的Ishikawa细胞和PTEN表达完整的HEC-1A细胞)增殖、凋亡、细胞周期及信号通路的影响。方法 MTT法检测抑制剂对细胞增殖的影响,金氏公式评价两抑制剂的协同效果;流式细胞仪检测细胞凋亡及周期分布;Western印迹检测细胞信号蛋白的表达。结果 RG-14260与雷帕霉素可抑制Ishikawa细胞增殖、诱导细胞凋亡、减少S期细胞数量、降低pAKT含量,二者联合应用呈协同效应;RG-14260与Rapamycin对HEC-1A细胞上述作用不明显。结论 PTEN基因缺失使相应信号通路抑制剂作用的子宫内膜癌细胞增殖明显受抑,细胞阻滞于G1期,细胞凋亡增加,对相关信号通路抑制剂的敏感性增加。

Effect of RG-14260 combined with Rapamycin on two human endometrial carcinoma cells in vitro

Objective To investigate the effects of RG-14260 alone or combined with Rapamycin on cell growth,cell apoptosis,cell cycle and signal pathway of two human endometrial carcinoma cells Ishikawa(PTEN-) and HEC-1A(PTEN+) in vitro.Methods MTT was used to determine the proliferative effects of two inhibitors on tumor cells.Jin′s formula was used to assess the synergistic effects between two inhibitors.Cell apoptosis and phase were detected by the flow cytometry.Western blot was used to measure the abundance of signal proteins.Results RG-14260 alone or combined with Rapamycin could inhibit cell proliferation,induce cell apoptosis,decrease S phase cells and lower the abundance of pAKT in Ishikawa cells.The effect of RG-14260 combined with Rapamycin was better than that of RG-14260 and Rapamycin alone.But in HEC-1A cells,these effects above were not obvious.Conclusions Loss of PTEN in endometrial carcinoma cells may improve the G1 phase cells and apoptosis effects,inhibit the cell proliferation,which due to the sensitivity of cells to related signal transduction inhibitors.