雷公藤红素逆转K562/A02细胞多药耐药的实验研究

目的探讨雷公藤红素逆转人慢性粒细胞白血病红白血病急变细胞株K562/A02多药耐药的效果。方法采用CCK-8法测定细胞的药敏性及耐药逆转性,应用流式细胞术检测细胞内ADM浓度、P-gp蛋白表达。结果雷公藤红素对K562/A02、K562的半数抑制率浓度（IC50）分别为（295.58±23.288）μmol/L、（411.59±26.551）μmol/L。K562/A02细胞对ADM的耐药性是K562细胞的79.78倍。细胞毒剂量的雷公藤红素作用后,ADM对K562/A02细胞的IC50显著下降（P〈0.05）,逆转倍数为117.860倍。细胞毒剂量（IC50）和非细胞毒剂量（IC10）的雷公藤红素处理后的K562/A02细胞内的ADM浓度显著增加（P〈0.05）,增加倍数分别为1.537倍和1.102倍。雷公藤红素能明显下调K562/A02细胞的P-gp表达。结论雷公藤红素对逆转K562/A02细胞的耐药性有一定的作用,其机制可能与下调P-gp表达有关。

The Experimental Studies of Celastrol on the Reversal of Multidrug Resistance in K562/A02 Cell Line

Objective To evaluate the effect of the celastrol on the reversal of multidrug resistance in K562/A02 cell line.Methods The sensitivity of K562 and K562/A02 to ADM and the reversal of drug resistance were determined with CCK-8 method.The concentration of intracellular ADM and P-gp expression were tested with flow cytometry(FCM).Results The IC50 of celastrol to K562/A02 and K562 cells were(295.58 ±23.288)μmol/L、(411.59±26.551)μmol/L.The resistance of K562/A02 cells to ADM was 79.78 times of K562 cells.After incubating with cytotoxic does of celastrol,the IC50 of ADM to K562/A02 decreased significantly(P<0.05),and the resistance was reversed by 117.860 times.After incubation of cytotoxic and non-cytotoxic does of celastrol,the intracellular concentration of ADM increased 1.537 and 1.102 times in K562/A02 cells(P<0.05).Celastrol could down-regulate P-gp expression obviously.Conclusion Celastrol could reverse the MDR of K562/A02 cell line in a certain extent,which may be attributed to down-regulating of P-gp expression.