米非司酮对子宫内膜癌细胞KLE和HHUA体外增殖和凋亡的研究

Effect of mifepristone on the proliferation and the apoptosis of endometrial carcinoma cell line KLE and HHUA in vitro

目的:探讨米非司酮(Mifepristone,MIF)对子宫内膜癌细胞系KLE和HHUA体外增殖、细胞周期和凋亡的影响。方法:KLE和HHUA在含不同浓度MIF(0、1×10-6、1×10-5、5×10-5、1×10-4mol/L)培养液中培养,应用MTT比色法、流式细胞术检测MIF对KLE和HHUA生长和细胞周期的影响,应用免疫组化SABC法检测肿瘤细胞ER、PR、Bcl-2和Bax的表达。结果:低浓度(≤10-6mol/L)MIF对KLE和HHUA细胞生长的抑制作用较弱,高浓度(5×10-5和1×10-4mol/L)MIF以时间-剂量依赖性方式显著抑制细胞生长。MIF阻滞细胞周期停滞于G1期,明显降低了S期细胞比例(P<0.05);MIF(≥10-5mol/L)显著降调ER、PR、Bcl-2表达,升调Bax表达,促进细胞凋亡。MIF对HHUA细胞的影响较KLE明显。结论:MIF通过阻滞细胞停滞于G1期和降低S期细胞比例,抑制KLE和HHUA细胞体外增殖;通过降调ER、PR、Bcl-2和升调Bax表达,促进KLE和HHUA细胞凋亡。

Objective： To study the effect of mifepristone（MIF） on the proliferation, cell cycle and apoptosis of the endometrial carcinoma cell lines KLE and HHUA, and to investigate the mechanism of MIF in vitro. Methods： Two endometrial carcinoma cell lines KLE and HHUA were cultured with different concentration （0, 1 × 10^-6 ,1 × 10^-5 ,5 × 10^-5 ,1 × 10^-4 mol/L） of MIF in vitro. MTT was used to examine the proliferation rate, FCM was adopted to determine the phase of cell cycle, and immunohistochemistry （SABC） was used to detect the expression of ER, PR, Bcl-2 and Bax. Results： Low dose （1 × 10^-6 mol/L）MIF weakly inhibited the proliferation of KLE and HHUA, and high dose （1 × 10^-5 - 1 × 10^-4 mol/L） MIF inhibited the proliferation of KLE and HHUA in a time-dose dependent fashion. MIF arrested the cell cycle at G1 phase and decreased the S phase fraction（SPF）. The expression of ER, PR and Bcl-2 significantly decreased, and the expression of Bax increased. The effect of MIF on HHUA was higher than that of KLE. Conclusion： Mifepristone inhibits the proliferation of KLE and HHUA in a dose-time dependent fashion in vitro by blocking cell cycle at G1 phase and decreasing the SPF , and induces the cell apoptosis by down-regulating the ER, PR , Bcl-2 and up-regulating the Bax.