Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells

Abstract

Previously we reported that the hypoxia-inducible factor-1alpha (HIF-1alpha) expression correlated with cell proliferation and apoptosis under 500 mM of CoCl2 treatment in a human gastric carcinoma cell line, MKN-1. Herein we report a similar correlation in other cell lines, MKN-45 and TMK-1. The dual-phase expression of HIF-1alpha was highest at 6 and 8 h of treatment in MKN-45 and TMK-1, respectively, while the peak in MKN-1 occurred at 4 h. The cell viability indices showed a similar dual phase to the HIF-1alpha expression, while the apoptotic indices started to increase as the level of the HIF-1alpha expression decreased. In our previous study, the FACS analysis showed a marked G2/M arrest and an increase of the pre-G1 area in MKN-1 after 36 h of treatment, whereas the G2/M arrest was not observed in MKN-45 and TMK-1. The expression of cell cycle and apoptosis-related proteins showed a correlation with the HIF-1alpha expression and the FACS results, which suggested that the level of HIF-1alpha correlated with proliferation and apoptosis in human gastric carcinoma cell lines with a possible cell-type specific pattern.