信号通路抑制剂对两株子宫内膜癌细胞生物学行为的影响

Impact of Signal Transduction Inhibitors on Biological Behaviours of Two Human Endometrial Carcinoma Cell Strains in Vitro

目的观察体外表皮生长因子受体(EGFR)信号通路抑制剂RG-14260(RG)单独及RG-14260联合mTOR信号通路抑制剂雷帕霉素Rapamycin(RA)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)生物学行为的影响。方法采用细胞形态学观察和细胞克隆形成法检测抑制剂对细胞增殖的影响;流式细胞仪检测细胞凋亡及周期分布;Transwell法检测细胞体外侵袭力的改变。结果 RG、RA均可明显增加Ishikawa细胞G1期细胞比例,降低S期细胞比例(P<0.05),RG、RA合用G1期细胞比例增加更明显(P<0.05),S期细胞比例下降更明显(P<0.01);RG、RA单用或联合使用均可诱导Ishikawa细胞凋亡,降低Ishikawa细胞存活率和侵袭力;RG、RA对HEC-1A细胞不敏感,经RG、RA单独或联合作用后各组HEC-1A细胞凋亡率、细胞存活率、侵袭力与相应处理的Ishikawa组细胞比较,差异均有统计学意义(P<0.01)。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生物学行为明显改变,对相关信号通路抑制剂的敏感性增加。

Objective To Investigate the impact of RG-14260 alone or combined with Rapamycin on biological behaviours of two human endometrial carcinoma cell strains,Ishikawa（PTEN-） and HEC-1A（PTEN＋）,in vitro.Methods Cell morphology observation and Clone formation test were used to determine the impact of the two inhibitors on proliferative behaviours of the tumor cells.Cell cycle and apoptosis status were detected using flow cytometry.Invasive ability of the cells was measured through the Transwell method.Results RG-14260 and Rapamycin,used alone or in combination increased the proportion of G1 phase cells（P0.05） and decreased the proportion of S phase cells（P0.05;RG/RA combination：P0.01）.Increase cell apoptosis rate,decreased survival rate,and invasive ability were found in Ishikawa cells treated with RG-14260 and Rapamycin,used alone or in combination.HEC-1A cells were less sensitive to RG-14260 and Rapamycin,compared with Ishikawa cells.Cell apoptosis rate,survival rate,and invasive ability between Ishikawa cells and HEC-1A cells showed significant differences after treatment（P0.01）.Conclusion Loss of PTEN in endometrial carcinoma cells may result in changes of biological behaviours,due to the increased sensitivity to inhibitors of related signial transduction pathway.