title: Adrenomedullin promotes angiogenesis in epithelial ovarian cancer through upregulating hypoxia-inducible factor-1α and vascular endothelial growth factor.
abstract: Adrenomedullin (ADM) is a multi-functional peptide related to many kinds of tumors. This study was aimed to investigate the role of ADM on angiogenesis in epithelial ovarian cancer (EOC) and its possible mechanism. The expressions of ADM, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and CD34 were examined by immunohistochemistry staining. The relationship among ADM, HIF-1α, VEGF and micro-vessel density (MVD) was assessed in 56 EOC tissues. CAOV3 cells were stably transfected with pcDNA-ADM (plasmid overexpressing ADM gene) or pRNA-shADM (small interfering RNA for ADM gene). Real-time PCR and western blot analysis were performed to detect the expressions of HIF-1α and VEGF. The MTT, transwell migration assay and in vitro tube formation analysis were used to evaluate the proliferation, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs) which were pretreated with ADM or ADM receptor antagonist ADM22-52. Our findings showed that ADM expression was positively correlated with the expressions of HIF-1α, VEGF or MVD in EOC. ADM upregulated expression of HIF-1α and VEGF in CAOV3 cells. ADM promoted HUVECs proliferation, migration and tube formation. In conclusion, ADM was an upstream molecule of HIF-1α/VEGF and it promoted angiogenesis through upregulating HIF-1α/VEGF in EOC.
authors.affiliation: Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Shenyang Forth People's Hospital, Shenyang 110001, Liaoning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, No. 401 Hospital of PLA, Qingdao 266071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Gynecology, Shenyang Forth People's Hospital, Shenyang 110001, Liaoning, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism* / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C104782:adrenomedullin (22-52); D053607:Adrenomedullin