环孢霉素 A 对 K562/DOX 细胞药物积聚和外排的影响

Effect of cyclosporin A on intracellular accumulation and efflux of drug in K562/DOX cells

目的：寻找克服肿瘤细胞多药耐药的方法。方法：以环孢霉素Ａ（ＣｓＡ）作为耐药逆转剂，用ＭＴＴ法体外药物敏感试验，观察ＣｓＡ对多药耐药白血病细胞株Ｋ５６２／ＤＯＸ的药物敏感性、细胞内药物的积聚和外排的影响。结果：ＣｓＡ可增强阿霉素（ＤＯＸ）对Ｋ５６２／ＤＯＸ的细胞毒作用，且存在剂量依赖关系。ＣｓＡ≥２μｇ／ｍｌ能较明显提高Ｋ５６２／ＤＯＸ对ＤＯＸ的敏感性。用２μｇ／ｍｌＣｓＡ处理后，Ｋ５６２／ＤＯＸ细胞内ＤＯＸ外排速度明显减慢，ＤＯＸ含量仅减少１２．３％，但对Ｋ５６２细胞内药物外排无影响。结论：ＣｓＡ能有效地减慢Ｋ５６２／ＤＯＸ细胞内ＤＯＸ外排速度，增加细胞内ＤＯＸ积聚。ＣｓＡ对Ｋ５６２细胞药物敏感性、细胞内药物外排和积聚均无影响。

Objective:To explore measures to overcome multidrug resistance of tumor cells.Methods:The effects of cyclosporin A (CsA) on drug sensitivity,intracellular drug accumulation and drug efflux in multidrug resistant human leukemic cell line K562/DOX were studied by MTT colorimetric assay and spectrofluorimetry.Results:CsA enhanced the cytotoxicity of doxorubicin (DOX) to K562/DOX, and when CsA≥2μg/ml the sensitivity of K562/DOX to DOX increased significantly.The efflux of DOX markedly decreased when K562/DOX cells were incubated with 2μg/ml CsA, while CsA had no effect on efflux of DOX in K562 cells.Conclusion:CsA could markedly decrease the efflux and enhance the intracellular accumulation of DOX in K562/DOX cells.