米托蒽醌对人卵巢癌COC1细胞增殖与凋亡的影响及其作用机制

目的：研究米托蒽醌（Mitoxantrone，MXT）对人卵巢癌COC1细胞体外增殖与凋亡活性，及凋亡相关基因Mcl-1表达的影响。方法应用四甲基偶氮唑蓝（MTT）法检测不同浓度的MXT对COC1细胞体外增殖活性的影响；流式细胞分析方法（FCM）定量检测不同浓度的MXT作用后COC1细胞的凋亡率；Western-blot检测active caspase-3蛋白和Mcl-1蛋白定量；RT-PCR检测Mcl-1 mRNA的表达变化。结果COC1细胞生长抑制率和凋亡率均随MXT浓度的增加递增（P〈0.05）；COC1细胞生长抑制率随MXT作用时间的延长而增高（P〈0.05）；active caspase-3蛋白水平随着MXT作用浓度增高递增（P〈0.05）；Mcl-1 mRNA和蛋白表达水平随着MXT作用浓度增高递减（P〈0.05）。结论米托蒽醌能抑制卵巢癌COC1细胞的增殖，诱导其凋亡，此作用可能与MXT抑制COC1细胞中的Mcl-1表达有关。

Proliferation and apoptosis of ovarian cancer cell COC1 induced by MXT and its in vitro Mechanism

Objective To investigate the effect of MXT on the proliferation and apoptosis of COC1 cell, and the influence of MXT on the expression of apoptosis related gene Mcl-1 and explore its mechanism.Methods The inhibition effect of different doses of MXT on COC1 cells was assayed with MTT test. COC1 cells apoptosis rate induced by different doses of MXT was detected by FCM method. Western-blotting was used to measure the protein level of active caspase-3 and Mcl-1. The mRNA expression of Mcl-1 in COC1 cells after being exposed to different doses of MXT were determined by RT-PCR. Results The COC1 cell growth inhibitory and apoptosis rate were increased with the increase of the concentration of MXT（P〈0.05）, The COC1 cell growth inhibitory rate also increased with the duration extension of MXT treatment（P〈0.05）. The protein level of active caspase-3 was upregulated with the increase of the concentration of MXT （P〈0.05）. The mRNA and protein expression level of Mcl-1 presented a significant negative correlation with the MXT concentration （P〈0.05）. Conclusion MXT can inhibit the proliferation of ovarian cancer cell COC1 and induce its apoptosis. This effect may be related to the inhibition of MXT on the mRNA expression of COC1 cell Mcl-1.