Reversal effect of triazole antifungal combined with adriamycin on multidrug resistance in leukemia cells / 白血病·淋巴瘤

ABSTRACT

Objective To investigate the reversal effect of triazole antifungal itraconazole,fluconazole combined with adriamycin on multidrug resistance in leukemia cells.Methods Human chronic myelogenous leukemia adriamycin resistant cell lines K562/ADR cells were incubated with itraconazole,fluconazole,or PSC833 (positive control) combined respectively with adriamycin.CCK-8 assay was used to assess cell proliferation of K562/ADR.The mean fluorescence intensity of intracellular ADR was measured by flow cytometry.The marker of DNA damage γH2AX was detected by Western blot.Results 1 μg/ml itraconazole and 0.5 μg/ml PSC833 can decrease K562/ADR IC50 of adriamycin from 38.30 μg/ml to 8.59 μg/ml and 24.64 μg/ml in a dose-dependent manner.K562/ADR cells were incubated with 1 μg/ml itraconazole or 0.5 μg/ml PSC833 combined respectively with adriamycin for 3 h and 6 h,the mean fluorescence intensity of intracellular ADR were increased 1.54-fold (3 h),1.50-fold (6 h) or 5.97-fold (3 h),5.83-fold (6 h).Itraconazole or PSC833 combined with adriamycin significantly increase the expression of γH2AX in K562/ ADR cells.Conclusion Itraconazole can recover adriamycin sensitivity of K562/ADR by increasing the concentration of intracelullar adriamycin and synergistically increasing DNA damage,but not for fluconazole.