Effect of Hypoxia-inducible Factor-1α Silencing on the Sensitivity of Human Brain Glioma Cells to Doxorubicin and Etoposide

Multidrug resistance (MDR) is a significant problem underlying the poor prognosis associated with gliomas. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is thought to induce the genes expression involved in MDR. To evaluate the effect of silencing HIF-1 alpha in human glioma T98G cells, cells were transfected with HIF-1 alpha-small interference RNA (HIF-1 alpha-siRNA) and cultured under hypoxic conditions. The effect of HIF-1 alpha-siRNA on HIF-1 alpha and multidrug resistance-associated protein 1 gene (MRP1) and protein levels was determined. Silencing rates of HIF-1 alpha were 90%, 85%, and 88% at 24, 48, 72 h post-transfection, respectively. Corresponding rates of HIF-1 alpha protein were 74.5%, 61.1% and 59.1%. MRP1 protein levels decreased by 7.6%, 36.8% and 45.2%. HIF-1 alpha-siRNA transfected cells were significantly more sensitive to doxorubicin and etoposide compared to non-transfected cells. These findings suggest that the HIF-1 alpha plays a role in mediating chemotherapeutic drug resistance in glioma cells. HIF-1 alpha silencing may prove to be an effective therapeutic means of treating gliomas.