2-甲氧基雌二醇抑制骨髓增生异常综合征SKM-1细胞增殖和诱导细胞凋亡

Effects of 2-methoxyestradiol on SKM-1 cell proliferation and apoptosis in myelodysplastic syndrome

目的探讨2-甲氧基雌二醇(2-ME)对骨髓增生异常综合征SKM-1细胞增殖和细胞凋亡的影响。方法常规培养的SKM-1细胞分为2-ME处理组与非处理对照组,SKM-1细胞分别与不同浓度2-ME(1、2、4和8μmol/L)和对照组共同培养,MTT法检测2-ME对SKM-1细胞增殖抑制作用;光学显微镜观察瑞氏-姬姆萨染色后的细胞形态;流式细胞术分析细胞周期和凋亡;荧光探针JC-1检测细胞线粒体膜电位(ΔΨm)。结果 2-ME对SKM-1细胞的生长抑制作用具有浓度和时间依赖性;光学显微镜下可见典型的凋亡细胞形态特征;SKM-1细胞被阻滞于G2/M期,表现为G0/G1期细胞和S期细胞逐渐减少,G2/M期细胞逐渐增多(P<0.05);2-ME降低细胞ΔΨm具有时间依赖性(P<0.05)。结论 2-ME对人骨髓增生异常综合征SKM-1细胞的增殖具有显著的抑制作用并可诱导细胞凋亡。其机制可能与细胞G2/M期阻滞和ΔΨm下调有关。

Objective To explore the effects of 2-methoxyestradiol（2-ME） on SKM-1 cell proliferation and apoptosis in myelodysplastic syndrome.Methods The SKM-1 cells were divided to 2-ME-treated group and non-2-ME-treated group as the control.After incubated with or without 2-ME at the concentrations of 1,2,4 and 8 μmol/L under standard condition,respectively,the inhibition of cell proliferation was assessed using MTT colorimetric assay.Cytomorphology was investigated under light microscope.Cell cycle status and the rate of apoptosis were evaluated by flow cytometry,and the mitochondrial membrane potential（ΔΨm） was observed under fluorescent microscope by fluorescent probe JC-1.Results 2-ME inhibited cell proliferation in the dose-and time-dependent manner and caused a sustained arrest at G2/M phase in SKM-1 cells.The typical apoptotic morphology was observed and the ΔΨm of SKM-1 cells was weakened in a pattern of time course by 2-ME（P0.05）.Conclusion 2-ME inhibits the SKM-1 cell proliferation and induces cell apoptosis in myelodysplastic syndrome,which may be related to the G2/M cell cycle arrest and the decrease of ΔΨm.