小分子Survivin抑制剂YM155对人子宫颈癌SiHa和ME-180细胞增殖、凋亡的影响及机制研究

Effects of Survivin Inhibitor YM155 on Proliferation and Apoptosis of SiHa and ME-180 Cervical Cancer Cells and the Mechanism Involved

目的探讨Survivin抑制剂YM155对子宫颈癌SiHa和ME-180细胞的作用及其机制。方法体外培养人子宫颈癌细胞SiHa和ME-180，不同浓度YM155处理SiHa和ME-180细胞，用MTT法检测其对细胞增殖的影响：流式细胞仪检测细胞凋亡情况：实时荧光定量PCR检测SurvivinmRNA的表达；蛋白免疫印迹法检测Survivin、PARP、caspase。3蛋白的表达；慢病毒介导敲减Survivin。结果YM155可抑制人子宫颈癌细胞SiHa和ME-180的增殖，且呈时间和剂量依赖性。有效浓度的YM155能显著诱导SiHa和ME-180细胞凋亡．同时能够降低SurvivinmRNA和蛋白的水平，激活PARP和easpase-3。结论YM155能够有效抑制人子宫颈癌SiHa和ME-180细胞增殖，并诱导其凋亡，其可能机制为抑制Survivin的表达，继而激活PARP／caspase凋亡信号通路。

Objective To explore the effects of YM155 on human cervical cancer cell lines Si- Ha and ME-180 and the associated mechanism. Methods Human cervical cancer cell lines SiHa and ME-180 were culturedin vitroand treated with different concentrations of YM155. Cell prolifera- tion inhibition rate was measured by MTT assay. The percentage of cell apoptosis was detected by flow cytometry. The mRNA level of survivin was detected by real-time quantitative PCR. The protein levels of surviving, PARP and caspase-3 were detected by Western blotting. Survivin in cells was knocked down by RNAi. Results YM155 inhibited SiHa and ME-180 cell proliferation in a dose- and time-dependent manner. YM155 of 100 nmol/L could induce significant apoptosis of SiHa and ME-180 cells, decrease mRNA and protein level of survivin and increase activated PARP and caspase-3 expression. Conclusion YM155 could effectively inhibit the proliferation of human cervical cancer cell lines SiHa and ME-180, and induce their apoptosis through downregulating survivin expression and activating caspase-3 pathway.