[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.


CONCLUSIONS
Sirolimus inhibited protein expression of HIF-1alpha, increased tumor apoptosis and decreased tumor growth.
Jiang
Hong-Yuan
HY
Department of Obstetrics and Gynecology, Obstetrics and Gynecologic Hospital of Fudan University, Shanghai 200011, China.
Feng
You-Ji
YJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D017239:Paclitaxel; D020123:Sirolimus