Vitamin E Succinate Overcomes Apoptosis Resistance in Multidrug-resistant K562/ADM Cells by Down-regulating Expression of mdr1 Gene and Its Product P-glycoprotein

Objective To explore the apoptotic effect of Vitamin E succinate(VES) on multidrug-resistant leukemia K562/ADM cells and the possible molecular mechanisms. Methods Human multidrug-resistant leukemia cell line K562/ADM overexpressing mdr1 gene was used as the target cells. The cell proliferating activity was assessed with a MTT colorimetric assay. The apoptosis of K562/ADM cells was investigated by optical and electronic microscopic morphology and Annexin V/PI staining. The expression of mdr1 and Caspase-3 mRNAs was detected with RT-PCR, and the P-glycoprotein (P-gp) expression and Caspase-3 activity were measured using flow cytometry. Results VES obviously inhibited the proliferation of K562/ADM cells. After VES-treatment, the typical apoptotic morphological changes were observed in K562/ADM cells, and the apoptosis rate of the cells by Annexin Ⅴ/PI staining was greatly increased. The expression of mdr1 mRNA and its product P-gp was markedly down-regulated, and the expression of Caspase-3 mRNA and Caspase-3 activity up-regulated in VES-induced K562/ADM cells. VES significantly enhanced the sensitivity of K562/ADM cells to adriamycin. Conclusion VES induces apoptosis of drug-resistant K562/ADM cells overexpressing mdr1/P-gp, the possible mechanism is reversal of the P-gp-mediated apoptosis resistance and drug-resistance via down-regulation of mdr1/P-gp expression in drug-resistant K562/ADM cells.