拓扑替康诱导人卵巢癌顺铂耐药细胞株COC1/DDP凋亡的研究

目的探讨拓扑替康(TPT)诱导人卵巢癌顺铂耐药株COC1/DDP凋亡的内在分子机制。方法采用透射电镜和TUNEL法观察TPT诱导COC1/DDP细胞凋亡的情况;采用RTPCR和Westernblot检测TPT对COC1/DDP细胞内bcl2、bax和caspase3基因表达的影响以及caspase3活性的改变。结果COC1/DDP细胞在TPT作用后出现典型的凋亡形态特征,且凋亡率由8.54%上升为19.31%(P<0.05);TPT不影响COC1/DDP细胞内bcl2mRNA表达,却明显增加baxmRNA和caspase3mRNA表达,并提高caspase3活性。结论TPT诱导COC1/DDP细胞凋亡可能依赖于细胞内bax蛋白增高和caspase3的活化。

The Study of Topotecan Induced Apoptosis in Cisplatin-resistant Human Ovarion Cancer Cell Lines COCl/DDP

Objective:To explore the molecular mechanism of topotecan-induced apoptosis in cisplatin-resistant human ovarian cancer cell line COC1/DDP. Methods:Transmission electron microscope(TEM) and TUNEL were employed to observe the apoptosis of COC1/DDP induced by topotecan. RT-PCR and Western blot were used to determine the expression of bcl-2,bax and caspase-3.Changes of the activity of caspase-3 were also recorded. Results:After incubated with topotecan, COC1/DDP cell demonstrated a typical apoptosis morphology The apoptotic rate increased from 8.54% to 19.31%(P<0.05).Although the expression of bcl-2 was not affected, the expression of bax and caspase-3 were upregulated and the caspase-3 activity was promoted in the course of COC1/DDP apoptosis when treated with topotecan. Conclusion:The increased bax expression and the promoted caspase-3 activity may play a crucial role in the apoptosis process of COC1/DDP induced by topotecan.