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