Objective:This study was to determine the anti-proliferation effects of using rapamycin or adriamycin alone or combination of them on human breast cancer MCF-7 cells exposed to normal oxygen concentration or hypoxic enviroment in vitro. Methods:MTT assay and flow cytometry were used to examine the influence of the drugs on cell proliferation and cell cycle of MCF-7 cells. MCF-7 cells were exposed to normal or hypoxic enviroment and treated with rapamycin or adriamycin alone or co-treated with rapamycin and adriamycin. Western blot analysis was used to assess the expression level of HIF-1α and pAkt. Results:Opposite to adriamycin,the effect of rapamycin on inhibiting cell proliferation of MCF-7 cells was enhanced when exposed to hypoxia compared with the effect under normal oxygen environment. Regardless of oxygen concentrations,no synergistic interaction was observed when rapamycin at clinical normal drug level(10 ng/ml) combined with adriamycin on MCF-7 cells. The MCF-7 cells treated with rapamycin alone were arrested at G1,while co-treated with rapamycin and adriamycin were arrested at G2. Hypoxia enhanced the expression levels of HIF-1α and pAkt,while rapamycin at 10 ng/ml had no influence on the expression levels of HIF-1α and pAkt. Conclusions:Hypoxia increased the sensitivity of rapamycin on MCF-7 cells,which may be caused by increasing pAkt expression subsequent to hypoxia.