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Hypoxia-inducible factor 1α (HIF-1α) correlated with tumor growth and apoptosis in ovarian cancer
  1. H. Jiang and
  2. Y. Feng
  1. Obstetrics and Gynecologic Hospital of Fudan University, Shanghai, China
  1. Address correspondence and reprint requests to: Youji Feng, Obstetrics and Gynecologic Hospital of Fudan University, Shanghai 200011, China. Email: yjfengobgyn{at}


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.

  • apoptosis
  • HIF-1α
  • ovarian cancer
  • VEGF

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