Oligomycin On The Multidrug Resistant Cell Line The K562/a02 Role Of Research

OBJECTIVE Oligomycin is a mitochondria-targeting agent, can inhibit mitochon-dria F0F1-ATPase. The aim of this study was to investigate the effects of oligomycin in human multidrug resistance leukemic K562/A02 cell line.METHODS MTT assay was used to test the toxicity of oligomycin and the chemosensitivity to adriamycin (ADM) in oligomycin-treated cells. Changes in the ADM and Rhodamine 123 accumulation, P-glycoprotein expression, rate of apopto-sis and the activity of caspase3,caspase8 and caspase9 were determined by flow cytometry.RESULTS Oligomycin elicited a dose-dependent cytotoxicity in K562 and K562/ A02 cells,and the IC50 were 33.66μg/mL and 12.24μg/mL, respectively. K562/A02 cells seem to be more susceptible to oligomycin than parental cells. Oligomycin can trigger apoptosis in K562 and K562/A02 cells.After 24 hours and 48 hours exposure to oligomycin at the dose of 25μg/mL, the apoptosis rate of K562/A02 cell line was higher than K562 cell line. Oligomycin can enhance the activity of caspase3 and caspase9, while the activity of caspase8 was not enhanced. By using caspase blocker Z-VAD-fmk, the activation of caspase3 and caspase9 were not inhibited completely. The inhibitory rates of K562 and K562/A02 cells caused by oligomycin were lower than 15% under the dose of 0.5μg/mL.After exposure to 0.5μg/mL oligomycin, the concentration of ADM and Rhodamine 123 were significantly increased while P-gp expression was not down-regulated in K562/A02 cells. Combined treatment with ADM and oligomycin elicited more cell death in multidrug resistance cell line. Oligomycin at 0.5μg/mL partly reversed the MDR of K562/A02 cells to ADM. The reverse efficiency to ADM was 1.80.CONCLUSION Oligomycin targeted mitochondria and can elicit apoptosis in K562/A02 cell line by mitochondria apoptotic pathway. Moreover, oligomycin can reverse the multidrug resistance of human leukemic K562/A02 cells to ADM in vitro, the possible mechanism is related to the inhibition activity of P-gp and increased accumulation of the chemotherapeutic agents in cells, while the expression of P-gp is not down-regulated.