HIF-1α inhibits IDH-1 expression in osteosarcoma

Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1 alpha in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1 alpha in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions. In addition, HIF-1 alpha was downregulated via lentiviral vector-mediated RNA interference (RNAi) in the MG-63 human osteosarcoma cell line. The results revealed that HIF-1 alpha was negatively correlated with IDH-1 in the osteosarcoma tissues. Both in MG-63 and 143B cell lines, the expression of HIF-1 alpha was increased while IDH-1 was decreased under a hypoxic condition compared to normal conditions. HIF-1 alpha downregulation promoted IDH-1 expression in the MG-63 cell line under either normal or hypoxic conditions. In conclusion, our findings suggest that HIF-1 alpha inhibits IDH-1 in osteosarcoma and consequently increases the incidence of osteosarcoma.