阿苯达唑抑制P-糖蛋白表达对耐顺铂卵巢癌细胞耐药性的影响

Albendazole reverses chemoresistance of cisplatin-resistant ovarian cancer cells by inhibiting P-glycoprotein expression

目的探讨阿苯达唑(albendazole,ABZ)通过抑制人耐顺铂卵巢癌SKOV-3/DDP细胞P-糖蛋白(P-glycopro-tein,P-gp)的表达对细胞耐药性的影响。方法在体外,用溴化二甲噻唑二苯四氨唑(MTT)比色法检测ABZ对SKOV-3/DDP细胞增殖的影响,求得抑制率为0%、25%、50%、75%所对应的ABZ浓度,并按抑制率将实验分为对照组,25%抑制浓度(IC25)组、半数抑制浓度(IC50)组和75%抑制浓度(IC75)组,每组给予相应浓度的ABZ处理,并按作用时间再将每组分为12、24、36 h亚组。分别用流式细胞仪检测各组细胞表面P-gp的表达。将不同浓度的顺铂(cisplatin,DDP)、表阿霉素(epirubicin,EPI)、5-氟尿嘧啶(5-fluorouracil,5-Fu)按照分组,联合和序贯ABZ处理细胞后,采用MTT比色法检测SKOV-3/DDP细胞体外增殖情况。结果 ABZ作用SKOV3/DDP细胞后使P-gp表达下降,呈浓度和时间依赖性。联合和序贯ABZ均能降低DDP、EPI和5-Fu对SKOV-3/DDP细胞的作用浓度,有浓度和时间依赖性,且联合作用优于序贯作用。结论在体外ABZ通过抑制SKOV-3/DDP细胞P-gp表达提高细胞对DDP、EPI、5-Fu的敏感性,并能逆转细胞的耐药性。

Objective To investigate the effect of albendazole（ABZ） on the chemoresistance of cisplatin-resistant human ovarian cancer SKOV-3/DDP cells by inhibiting P-glycoprotein（P-gp） expression.Method The effect of ABZ on the proliferation of SKOV-3/DDP cells was detected by methyl thiazolyl tetrazolium（MTT） colorimetry.According to the inhibition concentrations（IC） of 0%,25%,50% and 75%,the cells were then divided into 4 groups including a control group,an IC25 group,an IC50 group and an IC75 group.Moreover,each group was divided into three subgroups（12,24 and 36 h） based on the ABZ treatment time.P-gp expression was determined by flow cytometry.The proliferation of SKOV-3/DDP cells was detected by MTT colorimetry after the treatment with ABZ combined and sequential with cisplatin（DDP）,epirubicin（EPI） and 5-fluorouracil（5-Fu）.Results The expression of P-gp was decreased by ABZ in a dose-and time-dependent manner.Both combined and sequential with ABZ could decrease the effective concentrations of DDP,EPI and 5-Fu to SKOV-3/DDP cells in a dose-and time-dependent manner,and the effect of combination was better than that of sequential treatment.Conclusion Through down-regulating the expression of P-gp in SKOV-3/DDP cells,ABZ can increase the sensitivity of SKOV-3/DDP cell to DDP,EPI and 5-Fu,and reverse its chemoresistance.