Abstract. The exact mechanism behind the effect of hypoxiainducible factor-1· (HIF-1·) on the proliferation and/or apoptosis of carcinoma cells is still a matter of debate. We treated a human gastric carcinoma cell line, MKN-1 (mutant P53), with 500 μM CoCl 2 . A dual-phase pattern of HIF-1· expression with an increase until 4 h followed by a decrease until 36 h was observed. Immunocytochemistry showed that nuclear translocation was maximal at 4 h of treatment, while trypan blue staining showed a dual-phase pattern. Instead of G 1 /S arrest, FACS showed an increase in the pre-G 1 fraction and G 2 /M arrest that correlated with Cyclin-B1, SKP-2 and P27 expression. Starting at 6 h, the apoptotic index increased in a time-dependent manner, in correlation with the expression of HIF-1·, Bcl-2, Bcl-xL, Bax and cleaved-Caspase-9. Phosphorylation of Akt was inhibited by CoCl 2 treatment and LY294002 treatment inhibited HIF-1· expression in a dosedependent manner. These results suggested that the alteration of CoCl 2 -induced HIF-1· expression correlated with proliferation and apoptosis in MKN-1 cells. A possible role for the PI3K/Akt pathway was indicated in this model