干扰素和环孢霉素A 协同逆转K562/ ADM细胞对阿霉素的耐药性

  目的 观察干扰素(α-Interleron，α-IFN)和环孢霉素A(Cyclosporine A,CsA)对白血病K562/ADM细胞耐药性的协同逆转效应。方法 以多药耐药基因／P-糖蛋白(Muhidrug resistance gene／P-glycoprotein，mdrl／P-gp)超表达的K562／ADM细胞为靶细胞，MTT比色法检测药物的细胞毒效应；流式细胞仪检测细胞P-糖蛋白(P-glycoprotein，P-gp)表达水平；激光共聚焦显微镜观察细胞内阿霉素含量变化。结果 K562／ADM细胞对阿霉素呈高度耐药性，并与柔红霉素和鬼臼乙叉甙交叉耐药，但与CsA无交叉耐药。CsA和α-IFN单独或联合应用均对K562／ADM细胞的耐药性有较强的抑制效应。流式细胞仪和激光共聚焦显微镜分析发现α-IFN和CsA单独或联合均不能下调细胞mdrl/P-gp的表达，反而应激性地刺激耐药细胞P-gp的合成增加，但可抑制P-gp的功能、增加K562／ADM细胞内阿霉素的积聚。结论 α-IFN和CsA联合可协同逆转耐药白血病细胞的耐药性，其作用机制为抑制P-gp的功能而非下调mdrl／P-gp的表达水平。

Synergistic Reversal of Multidrug Resistance of Leukemia Cells by α-Interferon and Cyclosporine A

Objective 　To investigate the synergistic reversal effect of α-Interferon (α2IFN) and Cyclosporine A (CsA) on the multidrug-resistance of human leukemia K562/ ADM cells. Methods 　Human leukemia K562/ ADM cell that overexpresses P-glycoprotein ( P-gp) encoded by human multidrug resistance gene (mdr1) was used as the target cells. The α-IFN2 or / and CsA-administ rated K562/ ADM cells were analyzed for proliferation and sensitivity to adriamycin using MTT method , P-gp expression was determined by flow cytomet ry , and the int racellular adriamycin accumulation was examined by confocal laserscanning fluorescence microscopy. Results 　K562/ ADM cells were highly resistant to adriamycin , and cross-resistant to daunorubicin and etoposide , but uncross-resistant to CsA. CsA ,α-IFN orα-IFN plus CsA both significantly decreased the drug-resistance of K562/ ADM cells to adriamycin. Cytometric and confocal microscopic analysis showed that CsA and α-IFN did not down-regulate the mdr1/ P-gp expression in K562/ ADM cells , and cont rarily exerted a stress-activated increase of P-gp synthesis , but they could inhibit the pump function of P-gp and increase the adriamycin accumulation inK562/ADM cells.Conclusion 　α-IFN combined with CsA synergistically reverse the multidrug-resistance of K562/ ADM cells and increase their sensitivity to conventional chemotherapeutic agents via the inhibition of pump function of P-glycoprotein not down-regulation of it s expression.