title: Luteinizing hormone facilitates angiogenesis in ovarian epithelial tumor             cells and metformin inhibits the effect through the mTOR signaling pathway.
abstract: High levels of gonadotropin are a risk factor for ovarian cancer development. Aberrant gonadotropin levels benefit tumor angiogenesis, but the detailed mechanism is not clear. Therefore, the aim of this study was to investigate the molecular mechanism of high levels of luteinizing hormone (LH) on the promotion of tumor angiogenesis and to outline a feasible therapeutic strategy. Western blotting and immunofluorescence staining were used to determine the effect of LH on VEGF and slit2 expression and examine the signaling pathway involved in regulating the expression of both molecules. Real-time PCR was used to investigate the effect of metformin on LH induction of VEGF and slit2 expression. It was found that 50 mIU/ml LH significantly upregulated VEGF and slit2 expression, and activated the PI3K/AKT-mTOR signaling pathway. However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression. In conclusion, high levels of LH promote angiogenesis in ovarian cancer via the PI3K/AKT-mTOR pathway. However, metformin could inhibit tumor angiogenesis by blocking the mTOR signaling pathway.
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Gu
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone; D008687:Metformin; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D000098552:Slit Homolog 2 Protein; C546842:MTOR protein, human