Induction of hypoxia-inducible factor-1α inhibits drug-induced apoptosis in the human leukemic cell line HL-60

BACKGROUND: Leukemic cells originate from hypoxic bone marrow, which protects them from anti-cancer drugs. Although many factors that cause drug resistance in leukemic cells have been studied, the effect of hypoxia on drug-induced apoptosis is still poorly understood. METHODS: In this study, we examined the effect of hypoxia on anti-leukemic drug resistance in leukemic cell lines treated with cobalt chloride (CoCl(2)), a hypoxia-mimetic agent. Cellular proliferation was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and western blots were performed to investigate apoptosis-related proteins. RESULTS: Unlike its previously known apoptotic effect, the expression of HIF-1α increased the survival rate of human promyelocytic leukemia HL-60 cells when these cells were exposed to anti-leukemic drugs; these effects were mediated by heat-shock protein HSP70 and the pro-apoptotic protein Bax. CONCLUSION: These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.