Hypoxia-inducible factor 1α (HIF-1α) correlated with tumor growth and apoptosis in ovarian cancer

Abstract

The aims of this study were to investigate the hypoxia-inducible factor 1α (HIF-1α) protein inhibition and tumor growth by a molecular target of rapamycin inhibitor, rapamycin, in xenogeneic transplant model of ovarian cancer and to study the correlation of apoptosis with HIF-1α and vascular endothelial growth factor (VEGF) expression. Four groups of female nude mice were inoculated subcutaneous with SKOV-3 cells and treated with vehicle, rapamycin, paclitaxel, or rapamycin plus paclitaxel. The expressions of HIF-1α and VEGF and microvessel density (MVD) were assessed by immunohistochemistry. While messenger RNA (mRNA) expression of Glut1, bcl-2, and VEGF was studied by reverse transcription–polymerase chain reaction, and apoptosis of tumor cells was determined by terminal deoxynucleotidyl biotin-dUTP nick end labeling (TUNEL). The HIF-1α was expressed in epithelial ovarian cancer. There was a significant correlation between HIF-1α protein expression and VEGF or MVD. Tumor burden treated with rapamycin alone, rapamycin plus paclitaxel, and paclitaxel alone was reduced (47.91%, 51.03%, and 31.75%, respectively) compared with controls. The expression of HIF-1α was inhibited, and apoptotic index of tumor cell increased in rapamycin and rapamycin plus paclitaxel group. HIF-1α may upregulate VEGF expression both in mRNA and protein level. There is a positive correlation between HIF-1α and MVD. Rapamycin inhibits expression of HIF-1α and suppresses ovarian tumor growth. Our data suggested that a combination of HIF-1α inhibitor and chemotherapy could provide an effective approach for inhibiting tumor growth in ovarian cancer.