Inhibition of hypoxia-inducible factor 1? expression and tumor growth in SKOV3 ovarian cancer model by sirolimus / 中华妇产科杂志

ABSTRACT

Objective To investigate the inhibitory effect of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus on expression of hypoxia-inducible factor (HIF)1? protein and growth of ovarian carcinoma in an athymic mouse xenogeneic transplant model of ovarian cancer. Methods Four groups of female nude mice were inoculated subcutaneously with SKOV3 cells. After inoculation, mice were treated with saline, rapamycin alone, paclitaxel alone and sirolimus+paclitaxel. In each tumor protein expressions of HIF-1?,bcl-2 and apoptosis were determined by immunohistochemistry and RT-PCR. Results In sirolimus and sirolimus +paclitaxel groups protein expression of HIF-1? was inhibited. Tumor burden in rapamycin alone, sirolimus +paclitaxel, and paclitaxel alone was reduced by 47.9%( P 0.05) respectively compared with controls. Cell apoptosis inder in sirolimus alone(36), sirolimus +paclitaxel(40), paclitaxel alone(22),increased compared with control(15), while expression of bcl-2 decreased compared with control. Conclusion Sirolimus inhibited protein expression of HIF-1?, increased tumor apoptosis and decreased tumor growth.