Role of hypoxia-inducible factor-1α and survivin in enhancing radiosensitivity of breast cancer

Abstract

ObjectiveRadioresistance is associated with poor outcome in breast cancer patients. Hypoxia-inducible factor-1α (HIF-1α) and survivin are critical factors associated with radio-resistance. The aim of this study was to investigate the mechanisms of targeting HIF-1α and survivin in breast MDA-MB-231 cells and to understand their value in improving radiosensitivity in the patients. MethodsThe expression of HIF-1α and survivin in breast cancer patients was analysed by immunohistochemistry (IHC). Small interfering RNA (siRNA) was designed to target HIF-1α and survivin in cells, and the effects on proliferation, apoptosis, and radiosensitivity were measured. ResultsHIF-1α and survivin were expressed at higher levels in tumours than in normal tissues (P < 0.05). The expression of HIF-1α and survivin in recurrent tissues after radiotherapy tended to be elevated compared with tissues resected at the initial time of patients' diagnosis but there was no significant difference (P ≥ 0.05). The proliferation and apoptosis rates of cells in the RNA-interfered groups were significantly different from the blank control and NC-siRNA groups (P < 0.05). The proliferation rate of cells in each group did not change significantly with different doses of radiation (P ≥ 0.05), but the apoptosis rate in the RNA-interfered groups increased compared to the blank control and NC-siRNA groups (P < 0.05). Simultaneous targeting of HIF-1α and survivin had a stronger effect on cancer cell proliferation, apoptosis and radiosensitivity of cancer cells than individual interference of HIF-1α or survivin alone (P < 0.05). ConclusionCombinatorial therapeutic intervention of HIF-1α and survivin may be a potential strategy to improve the radiosensitivity of breast cancer patients.