[Inhibition of hypoxia-inducible factor 1alpha expression and tumor growth in SKOV3 ovarian cancer model by sirolimus].

Objective: To investigate the inhibitory effect of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus on expression of hypoxia-inducible factor (HIF)1alpha 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-1alpha, bcl-2 and apoptosis were determined by immunohistochemistry and RT-PCR.

Results: In sirolimus and sirolimus + paclitaxel groups protein expression of HIF-1alpha was inhibited. Tumor burden in rapamycin alone, sirolimus + paclitaxel, and paclitaxel alone was reduced by 47.9% (P < 0.05), 51.0% (P < 0.05), and 31.8% (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-1alpha, increased tumor apoptosis and decreased tumor growth.