TSA增强人卵巢癌顺铂耐药株C13对顺铂敏感性的体外研究

TSA increases the sensitivity of human ovarian cancer cell line C13 * to cisplatin in vitro

目的:本研究探讨组蛋白去乙酰化酶抑制剂trichostatin A(TSA)联合化疗药物顺铂(DDP)处理人卵巢癌顺铂耐药株C13*的协同效应。方法:MTT法观察TSA、DDP、TSA+DDP对C13*细胞增殖的影响;克隆形成实验分别检测DDP、TSA+DDP处理C13*的克隆形成率;流式细胞仪检测凋亡和分析细胞周期;Hochest33258观察凋亡细胞形态。结果: 40 nmol／L TSA处理C13*12 h,细胞的凋亡率为2．99％,MTT显示生长未受明显影响;TSA+DDP组较DDP组C13*对DDP的作用更为敏感,在DDP为20～30μmol／L时差异显著(P<0．05)。结论:一定浓度的TSA和DDP联合应用可以增强人卵巢癌顺铂耐药株C13*对顺铂的敏感性。

Objective：To investigate the synergistic effects of a histone deacetylase inhibitor, trichostatin A （TSA）, combined with cisplatin （DDP） on cisplatin resistant ovarian epithelial cancer cell line C13 ＊ . Methods： The effects of TSA and/or DDP on the proliferation of C13 ＊ cells were detected by MTT assay. The clonogenic rate of C13 ＊ cells after DDP or TSA＋ DDP treatment was determined by clonogenic test. Flow cytometry analysis was used to detect cell apoptosis and analyze cell cycle. The morphology of apoptotic cells was observed by Hochest 33258 staining. Results： The apoptotic rate of C13 ＊ cells was 2.99% after treatment with TSA 40 nmol/L for 12 h. MTT assay showed that TSA treatment had no significant influence on cell proliferation. Preincubation with a subtoxic concentration of TSA markedly sensitized C13 ＊ cells to DDP treatment cony pared with those treated with DDP only. The difference was significant when DDP was in the range of 20-30 mmol/L （P〈 0.05）. Conclusion：Combined treatment with subtoxic concentration of TSA and DDP can increase the sensitivity of DDP-resistant human ovarian cancer cell line C13 ＊ in vitro.