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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 investigate the anti-cisplatin (DDP) effect of cisplatin-resistant human ovarian cancer cell line SKOV3 / DDP using medroxyprogesterone acetate (MPA) in vitro and its mechanism of action. Methods: The cytotoxic effect of MPA on SKOV3 / DDP was detected by MTT method. The cytotoxicity of MPA to this cell line was determined as reversal dose. The non-cytotoxic dose of MPA combined with DDP After treated with SKOV3 / DDP, the cell cycle and apoptosis were detected by flow cytometry (FCM). Results: MPA concentration of greater than 7.50 g / L SKOV3 / DDP cells have different degrees of inhibition, and in a dose-dependent manner. MPA concentration of less than 15.85 g / L, the cell growth was no significant effect (cell survival were> 90%), so the choice of 15.00 g / L as a reversal dose. DDP combined 15.00 g / L MPA for 24,48,72 h, the IC50 of cisplatin decreased to (57.72 ± 0.48) g / L, (13.39 ± 0.21) g / L, (7.93 ± 0.18) g / L , The reversal multiple were 1.22,1.90,2.44 times. DDP combined with MPA in SKOV3 / DDP cells, the cell cycle arrest in G0 / G1 phase, S phase cells decreased, and can increase the rate of apoptosis of drug-resistant cells. CONCLUSION: MPA can reverse DDP-induced drug resistance in ovarian cancer, which may reverse the mechanism of drug resistance in order to promote cell apoptosis and arrest cell cycle progression.