环孢菌素A与细胞因子联合逆转白血病多药耐药性的体外研究

目的 探讨环孢菌素Ａ（ＣｓＡ）联合细胞因子对耐药细胞系Ｋ５６２／Ａ０２的逆转作用,方法 以甲基四唑蓝法测定柔红霉素（ＤＮＲ）的细胞毒性,用流式细胞仪技术测定细胞内罗丹明（Ｒｈ１２３）浓度,用ＲＴ－ＰＣＲ及ＪＳＢ－１抗体分别检测多药耐药（ＭＤＲ１）ｍＲＮＡ及其Ｐ糖蛋白的表达。结果 １μｍｏｌ／ＬＣｓＡ,５００Ｕ／ｍｌ干扰素２００Ｕ／ｍｌ白介素２（ＩＬ－２）均能增加ＤＮＲ对耐药细胞系Ｋ５６２／Ａ０２的

In vitro reversal effect of cyclosporin A in combination with cytokines on multidrug resistant cell line K562/A02

OBJECTIVE: To explore the reversal effect of cyclosporin A(CsA) in combination with cytokines on multidrug resistant cell line K562/A02. METHOD: The cytotoxicities of daunorubicin(DNR) were assayed by MTT method. Intracellular rhodamine(Rh123) concentration was measured by flow cytometry. P-glycoprotein(p-gp) expression was analyzed for staining with monoclonal JSB-1. Mdr1 mRNA expression was detected by RT-PCR. RESULTS: The cytotoxicities of DNR to K562/A02 were enhanced by 1 mumol/L CsA, 500 U/ml IFN-alpha and 200 U/ml, IL-2 respectively, and their IC50 was (3.78 +/- 0.03), (13.77 +/- 0.38) mu/ml, (18.5 +/- 0.60) micrograms/ml. Their reversal effect was 6.70, 1.84 and 1.37 times than that of K562/A02. But IC50 of combined CsA and IFN-alpha was (1.71 +/- 0.19) micrograms/ml; its reverse effect increased in 14.8 times. The combination could increase intracellular Rh123 accumulation significantly as compared with either of them alone, but p-gp and mdr1 mRNA expression were not decreased obviously. CsA in combination with IL-2 didn't show a synergistic effect. CONCLUSION: Mdr could be partially reversed by cytokines or low doses CsA(1 mumol/L), but the combination of CsA and IFN-alpha showed a greater synergistic reversal interaction.