来曲唑通过下调bcl-2和上调caspase-3的表达促进人子宫肌瘤细胞调亡

Letrozole Inhibits Cells Apoptosis Through the Down-Regulation of Bcl-2 Expression and Up-Regulation of Caspase-3 Expression in Human Uterine Leiomyoma Cells

目的探讨来曲唑对人子宫肌瘤细胞增殖和凋亡以及bcl-2和caspase-3表达的影响。方法来曲唑处理原代培养的人子宫肌瘤细胞,用MTT法测定细胞生长曲线,流式细胞术测定细胞凋亡率,放射免疫法测定培养基中雌二醇水平,用实时定量聚合酶链反应和蛋白印迹检测bcl-2和caspase-3表达。结果来曲唑呈浓度和时间依赖性抑制子宫肌瘤细胞的增殖,降低子宫肌瘤细胞的凋亡率,同时呈浓度依赖性降低子宫肌瘤细胞雌二醇的分泌。来曲唑呈浓度依赖性降低bcl-2的表达,增加caspase-3的表达。结论来曲唑抑制子宫肌瘤细胞的增殖,促进其凋亡,其机制可能与来曲唑减少雌二醇的分泌、降低bcl-2表达和增加caspase-3表达有关。

Objective To explore the effect of letrozole on proliferation,apoptosis and the expression of bcl-2 and caspase-3 in human uterine leiomyoma cells.Methods Primary culture human leimyoma cells were treated with letrozole（10-8,10-7,10-6 and 10-5 mol/L） for 24,48 and 72 hours and MTT assay was used to detect the growth curve.The rates of apoptosis of cells were measured by flow cytometry.The level of estradiol in culture medium was measured by radio-immunity assay.The expression of bcl-2 and caspase-3 were detected by Real-time PCR and Western blot.Results The proliferations of uterine leiomyoma cells were significantly inhibited and the rates of apoptosis of uterine leiomyoma cells were markedly increased by treatment with 10-7,10-6 and 10-5 mol/L letrozole for 48 and 72 hours in a dose-dependent and time-dependent manner.The levels of estradiol in culture medium were decreased in a dose-dependent manner by treatment with 10-7,10-6 and 10-5 mol/L letrozole for 72 hours.The expression of bcl-2 was significantly decreased and the expression of caspase-3 was markedly increased by letrozole in a dose-dependent manner.Conclusions Letrozole inhibits the proliferation,promotes the apoptosis,which mechanism may be related to the decrease of estradiol secretion,the decrease of bcl-2 expression and the increase of caspase-3 expression induced by letrozole in human uterine leiomyoma cells.