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

Abstract

Abstract: AIM: To discuss the role of the reactive oxygen species (ROS) and relationshiPbetween ROS and expression of mdr1/P-gPduring apoptosis induced by arsenic trioxide (As₂O₃) in multidrug-resistant human leukemia K562/ADM cells.METHODS: The cell proliferating activity was assessed with MTT assay.The cell apoptosis was determined by annexin Ⅴ/PI staining.ROS was labelled by DCFH-DA and examined by flow cytometry.Expression of mdr1 mRNA and P-gPwere detected by RT-PCR and flow cytometry, respectively.The contents of adriamycin (ADM) were detected by flow cytometry.RESULTS: As2O3 inhibited K562/ADM cells growth effectively, and the apoptosis rate of the cells by Annexin Ⅴ/PI staining was obviously increased.During apoptosis induced by 2 to 5 μmol·L^-1As₂O₃, the level of ROS was markedly decreased;the expression of mdr1 mRNA and P-gPwere significantly down-regulated, and the function of P-gPwas restrained so that the content of ADM increased in the cells.CONCLUSION: As₂O₃inhibits 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-gPexpression via declines of ROS activity.

Key words: arsenic trioxide, multi-drug resistance, apoptosis, reactive oxygen species, mdr1, P-gp

CLC Number:

ZHANG Ya-li, WEI Hu-lai, GUO Lu. Reactive oxygen species play an important role in arsenic trioxide-induced apoptosis of multi-drug resistant K562/ADM cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(12): 1375-1379.

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