Reactive oxygen species play an important role in arsenic trioxide-induced apoptosis of multi-drug resistant K562/ADM cells

AIM: To discuss the role of the reactive oxygen species (ROS) and relationship between ROS and expression of mdr1/P-gp during apoptosis induced by arsenic trioxide (As_2O_3) in multidrug-resistant human leukemia K562/ADM cells. METHODS: The cell proliferating activity was assessed with MTT assay. The cell apoptosis was determined by annexinⅤ/PI staining. ROS was labelled by DCFH-DA and examined by flow cytometry. Expression of mdr1 mRNA and P-gp were detected by RT-PCR and flow cytometry, respectively. The contents of adriamycin (ADM) were detected by flow cytometry. RESULTS: As_2O_3 inhibited K562/ADM cells growth effectively, and the apoptosis rate of the cells by AnnexinⅤ/PI staining was obviously increased. During apoptosis induced by 2 to 5 μmol·L~ -1 As_2O_3, the level of ROS was markedly decreased; the expression of mdr1 mRNA and P-gp were significantly down-regulated, and the function of P-gp was restrained so that the content of ADM increased in the cells. CONCLUSION: As_2O_3 inhibits the proliferation activity and reverses phenomena of P-gp-mediated multidrug-resistance and apoptosis resistance in drug-resistant K562/ADM cells. The possible mechanism is down-regulation of mdr1/P-gp expression via declines of ROS activity.