摘要
目的:应用甲羟孕酮(Medroxyprogesterone Acetate,MPA)体外逆转人卵巢癌顺铂耐药细胞株SKOV3/DDP的耐顺铂(cisplatin,DDP)效应,并对其作用机制进行初步探讨。方法:采用四甲基偶氮唑蓝(MTT)法检测MPA对SKOV3/DDP的细胞毒作用,确定MPA对此细胞株的非细胞毒性剂量作为逆转剂量,同法测定非细胞毒性剂量MPA联合DDP作用后SKOV3/DDP对顺铂耐药性的变化,采用流式细胞技术(FCM)检测细胞周期及凋亡情况。结果:单用MPA浓度大于7.50 g/L时对SKOV3/DDP细胞有不同程度的抑制作用,且呈剂量依赖性。MPA浓度小于15.85 g/L时,其对细胞生长无明显抑制作用(细胞存活率均>90%),因此选用15.00 g/L作为逆转剂量。DDP联合15.00 g/L的MPA作用24、48、72 h后,顺铂的IC50分别下降至(57.72±0.48)g/L、(13.39±0.21)g/L、(7.93±0.18)g/L,逆转倍数分别为1.22,1.90,2.44倍。DDP与MPA联合作用于SKOV3/DDP细胞,使其细胞周期阻滞于G0/G1期,S期细胞比例下降,并可以增加耐药细胞的凋亡率。结论:MPA可以逆转DDP引发的卵巢癌耐药,其可能的逆转耐药机制为促进细胞的凋亡,阻滞细胞周期进程。
Objective：To reverse the drug resistance of human ovarian carcinoma cell line SKOV3/DDP to cisplatin by medroxyprogesterone acetate（MPA） in vitro,and explore the mechanism preliminarily. Methods：MTT method was used to detect the cytotoxicity of MPA to SKOV3/DDP cells,the non-cytotoxic dose was selected as reversible dose,the change of drug resistance of SKOV3/DDP to cisplatin was detected after treated with MPA of non-cytotoxic dose combined with cisplatin,flow cytometry was used to detect cell cycle and apoptosis. Results：When the concentration of MPA was higher than 7.50 g/L,MPA inhibited SKOV3/DDP cells of varying degrees,showing a dose-dependent manner.When the concentration of MPA was lower than 15.85g/L,MPA had no apparent inhibiting effect on cell growth（cell survival rate〉90%）,thus,15.00 g/L was selected as reversible dose.After treating SKOV3/DDP cells by cisplatin combined with MPA（15.00 g/L） for 24,48 and 72 hours,the IC50 values of cisplatin decreased to（57.72±0.48） g/L,（13.39±0.21） g/L and（7.93±0.18） g/L,respectively;the reversal multiples were 1.22,1.90 and 2.44,respectively.The cell cycle of SKOV3/DDP cells was arrested at G0/G1 phase after treated with cisplatin combined with MPA,the proportion of SKOV3/DDP cells at S phase decreased,and the apoptosis rate increased. Conclusion：MPA can reverse the drug resistance of ovarian carcinoma to cisplatin,the possible mechanism is MPA can promote cell apoptosis and arrest the course of cell cycle
出处
《中国妇幼保健》
CAS
北大核心
2011年第11期1699-1701,共3页
Maternal and Child Health Care of China
关键词
卵巢癌
甲羟孕酮
耐药逆转
凋亡
Ovarian carcinoma
Medroxyprogesterone acetate
Drug resistance reversal
Apoptosis
