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Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, Liaoning, China
Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China
* Author to whom correspondence should be addressed.
Received: 14 February 2013; in revised form: 18 April 2013 / Accepted: 24 April 2013 / Published: 7 May 2013
Abstract: Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is associated with obesity, insulin resistance and inflammation. Recently, resistin has been postulated to play a role in angiogenesis. Here, we investigated the hypothesis that resistin regulates ovary carcinoma production of vascular endothelial growth factor (VEGF) and the angiogenic processes. We found that in human ovarian epithelial carcinoma cells (HO-8910), resistin (10–150 ng/mL) enhanced both VEGF protein and mRNA expression in a time- and concentration-dependent manner, as well as promoter activity. Furthermore, resistin enhanced DNA-binding activity of Sp1 with VEGF promoter in a PI3K/Akt-dependent manner. PI3K/Akt activated by resistin led to increasing interaction with Sp1, triggering a progressive phosphorylation of Sp1 on Thr453 and Thr739, resulting in the upregulation of VEGF expression. In an in vitro angiogenesis system for endothelial cells (EA.hy926) co-cultured with HO-8910 cells, we observed that the addition of resistin stimulated endothelial cell tube formation, which could be abolished by VEGF neutralizing antibody. Our findings suggest that the PI3K/Akt-Sp1 pathway is involved in resistin-induced VEGF expression in HO-8910 cells and indicates that antiangiogenesis therapy may be beneficial treatment against ovarian epithelial carcinoma, especially in obese patients.
Keywords: resistin; vascular endothelial growth factor (VEGF); Sp1; phosphoinositide 3-kinase (PI3K)/Akt
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MDPI and ACS Style
Pang, L.; Zhang, Y.; Yu, Y.; Zhang, S. Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells. Int. J. Mol. Sci. 2013, 14, 9751-9766.
Pang L, Zhang Y, Yu Y, Zhang S. Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells. International Journal of Molecular Sciences. 2013; 14(5):9751-9766.
Pang, Li; Zhang, Yi; Yu, Yu; Zhang, Shulan. 2013. "Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells." Int. J. Mol. Sci. 14, no. 5: 9751-9766.