title: Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro.
abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pang
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Fang
authors.initials: F
authors.lastname: Wen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000080866:Nucleobindins; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D044967:Serum; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: Apoptosis; Mammalian target of rapamycin (mTOR); Nesfatin-1; Ovarian epithelial carcinoma; Proliferation; RhoA/Rho-associated coiled coil-containing protein kinase (ROCK)