The exact mechanism behind the effect of hypoxia-inducible factor-1α (HIF-1α) 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 CoCl2. A dual-phase pattern of HIF-1α 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 G1/S arrest, FACS showed an increase in the pre-G1 fraction and G2/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-1α, Bcl-2, Bcl-xL, Bax and cleaved-Caspase-9. Phosphorylation of Akt was inhibited by CoCl2 treatment and LY294002 treatment inhibited HIF-1α expression in a dose-dependent manner. These results suggested that the alteration of CoCl2-induced HIF-1α expression correlated with proliferation and apoptosis in MKN-1 cells. A possible role for the PI3K/Akt pathway was indicated in this model of hypoxia.

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