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.