LHRH拮抗剂Cetrorelix对子宫内膜癌细胞生长周期的影响及其机理

The effect of LHRH antagonist cetrorelix on the cell cycle of endometrial carcinoma and its mechanism

目的 :研究LHRH拮抗剂Cetrorelix对子宫内膜癌细胞生长周期及周期相关蛋白的影响 ,探讨其抑制内膜癌细胞生长的机理。方法 :用流式细胞仪细胞周期分析及Westernblotting蛋白分析法 ,研究在Cetrorelix的作用下子宫内膜癌细胞系HEC 1A细胞生长周期及相关周期蛋白的改变。结果 :1 0 -5mol/LCetrorelix可导致HEC 1A细胞生长停滞于G2 /M期 ,而与G2 /M期停滞相关的p5 3 ,磷酸化p5 3 (phospho p5 3 ) (丝氨酸 3 92 )及磷酸化cdc2 (phospho cdc2 ) (酪氨酸 1 5 )蛋白水平均显著增高。结论 :Cetrorelix抑制内膜癌细胞增殖作用的机理是结合细胞表面受体后引起一系列抑制性信号传递 ,导致细胞周期停滞于G2 /M期 ,主要表现为G2 期停滞。其中p5

Objective:To study the mechanism of the inhibitive effects of LHRH antagonist cetrorelix on the growth of endometrial cancer.Methods:Cell culture,flow cytometry and Westernblotting were used to investigate the alterations of cell cycle progression and some cell cycle related proteins including P53,cdc2 and cyclin B1 in endometrial cancer cell line HEC 1A when treated with cetrorelix.Results:Cetrorelix at 10 -5 mol/L arrested the cell cycle in HEC 1A cells at G 2/M phase.The levels of some cell cycle regulatory proteins including P53,phospho p53(Ser392) and phospho cdc2(Tyr15) were significantly elevated.Conclusions:LHRH antagonist cetrorelix may inhibit the growth of endometrial cancer cell by inducing cell cycle G 2/M phase arrest and G 2 phase is mainly involved.The arrest may be the result of the activation of P53 protein and the phosphorylated inactivation of cdc2 protein.