Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse of lung cancer

Abstract

Hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) play important roles in tumor angiogenesis. We examined the effect of endostar, an inhibitor of angiogenesis on the expression of HIF-1 and VEGF and on angiogenesis and radio sensitization. Flow cytometry (FCM) was used to evaluate the cell cycle phase distribution affected by endostar. The cell growth inhibiting rate was detected by methyl thiazolyl tetrazolium (MTT). Hoechst staining displayed the apoptotic cells, the expression of HIF-1 and VEGF was determined by enzyme linked immunosorbent assay (Elisa). To explore the anti-tumor efficacy in vivo, Lewis lung cancer models were established in the hind limb of female C57BL/6J mice by subcutaneous transplantation. We calculated the tumor inhibitory rate and detected the microvessel density (MVD) and VEGF expression by Immunohistochemistry. Whether in vitro or in vivo, endostar in combination with radiotherapy (RT) had the most significant inhibitory effect. Endostar had the function of block cell periods on A549 and stopped the cell cycle at G2/M and S periods. It also decreased the expression of HIF-1 and VEGF induced by radiotherapy. Endostar combined with irradiation had synergistic anti-tumor effect. And the mechanism may be that endostar can arrest the cell cycle at stage of G2/M and S, thereby, inhibiting the proliferation of tumor cells. In addition, the inhibition of HIF-1 and VEGF which play important role in resistant of radiotherapy may contribute to the synergistic effect.