环胞菌素A逆转数种人类胶质瘤细胞多药耐药性的体外实验研究

Experimental Study of Reversal of Mutidrug Resistance by Cyclosporin A in Various Human Gliom Cell Lines

目的 探讨环胞菌素A体外逆转人类胶质瘤细多药耐药性的作用及其机理。方法 采用有MDR1和MRP表达的人类胶质瘤细系 ,通过放射自显影观察应用环胞菌素A前后抗癌药物在细胞内的积累与外排量。结果 在有MDR1和MRP表达的人类胶质瘤细胞系中 ,加入环胞菌素A后细胞内抗癌药物积累量显著增加 (P <0 .0 5 )。结论 环胞菌素A可增加耐药细胞对抗癌药的敏感性 ,在体外能有效地逆转入类胶质瘤细胞的多药耐药性。其作用机制除了与细胞膜上的P -糖蛋白竞争性结合、抑制药物外排 ,对MRP过度表达的胶质瘤细胞系也有逆转作用 ,这可能与细胞类型有关。

Objective To explore the effects and mechanisms of reversing action on multidrug resistance by cyclosporin A in vitro in various human glioma cell lines overexpressing MDR 1 and MRP.Methods By the method of Rediolabeled oxorubicin,the human gliom cell lines were used to investigate the potential differences in the accumulation and efflux of antitumor drugs before and after the use of cyclosporin A. Results The accumulation of intracellular antitumor drug increased obvously after the use of cycosporin A in the human glioma cell lines overepressing MDR and MRP ( P >0.05). Conclusion cyclosporin A can increase the sensitization of antitumor drugs and reverse mutidrug resistance in the human glioma cell in vitro,The mechanisms of cyclosporin A are not only due to competition binding with p\|glycoprotin and inhibition outward transport of the antitumor drugs,but also reversal of multidrug resistance which is dependent on cell tepes in human glioma cell lines.