穿琥宁对COC1/DDP顺铂耐药性的逆转作用

Reversal effect of potassium dehydroand rograpolide succinate on the resistance to cisplatin in COC1/DDP cells

目的:建立人卵巢癌顺铂耐药细胞株COC1/DDP,探讨穿琥宁对COC1/DDP顺铂耐药性的逆转作用及其机制。方法:采用逐步递增顺铂浓度、体外间歇诱导法建立COC1/DDP;CCK-8试剂盒(CellCounting Kit-8)检测穿琥宁对COC1/DDP顺铂耐药性的逆转作用;GSH和GSSG试剂盒检测细胞内GSH的水平;高效液相色谱测定细胞内顺铂的含量。结果:历时5个月建立的COC1/DDP细胞株对顺铂耐药性稳定,耐药指数为9.44,对卡铂、长春新碱和阿霉素有不同程度的交叉耐药性。穿琥宁对COC1/DDP的顺铂耐药性有逆转作用,逆转倍数达到5.63倍。与COC1比较,COC1/DDP细胞内GSH水平增高,顺铂含量下降,但经穿琥宁干预后,COC1/DDP胞内的GSH水平降低,顺铂的含量增加(P<0.01)。结论:穿琥宁对COC1/DDP的顺铂耐药性有逆转作用,其机制可能与干预COC1/DDP细胞内GSH/GST-π解毒系统,增加COC1/DDP细胞内顺铂的含量有关。

Objective： To establish a cisplatin-resistant ovarian cancer cell line,COC1/DDP cells,and to observe the reversal effect and its mechanism of potassium dehydroand rograpolide succinate in COC1/DDP cells.Methods： COC1/DDP cell line was established by gradually increasing the concentration of cisplatin and intermittent-induced method to COC1 cell line in vitro.Reversal effect of potassium dehydroand rograpolide succinate on COC1/DDP cell proliferation was detected by Cell Counting Kit-8.The level of GSH was determined by GSH and GSSG kits.The content of cisplatin was detected by HPLC.Results： COC1/DDP cells with stable resistance to cisplatin were developed after induction for 5 month.They not only had a resistance index of 9.44,but also exhibited cross-resistance to carboplatin,vincristine and adriamycin at different degrees.Potassium dehydroand rograpolide succinate reversed the resistance of COC1/DDP cell line and the reversal fold was 5.63.Compared to the COC1 cells,the level of GSH increased but the cisplatin content decreased in COC1/DDP cells.However,potassium dehydroand rograpolide succinate decreased the level of GSH and increased cisplatin content in COC1/DDP cells（P〈0.01）.Conclusion： Potassium dehydroand rograpolide succinate exhibits the reversal effect on COC1/DDP cells;its mechanism may relate to increasing the content of cisplatin by affecting GSH/GST-π detoxification systems in COC1/DDP cells.