title: Promotive effects of bone morphogenetic protein 2 on angiogenesis in hepatocarcinoma via multiple signal pathways.
abstract: The effects of Bone morphogenetic protein 2 (BMP-2) on the angiogenesis of hepatocellular carcinoma have not yet been observed and its molecular mechanisms is not clear. We first constructed the recombinant lentivirus vectors expressing small hairpin RNA against BMP-2 gene (LV-SH-BMP2) and the recombinant lentivirus vectors over-expressing BMP-2 (overexpression-LV-BMP2), and then the two recombinant lentivirus vectors were respectively transfected into Hep G2 cells. The Hep G2 cells transfected with LV-SH-BMP2 or overexpression-LV-BMP2 were respectively co-cultured with human umbilical vein endothelial cells (HUVECs) to observe the effects of BMP-2 on HUVECs. The effect of BMP-2 on tumor microvessel density (MVD) was examined. The abilities of proliferation, migration and angiogenesis were significantly inhibited in the HUVECs co-cultured with BMP-2 knockdown Hep G2 (all P < 0.05), but significantly enhanced in the HUVECs co-cultured with BMP-2 overexpression Hep G2 (all P < 0.05). MVD was significantly increased in overexpression-LV-BMP2-transfected Hep G2 tumor, but decreased in LV-SH-BMP2-transfected Hep G2 tumors. The protein expressions of VEGF, p-P38, p-ERK, p-AKT, p-m-TOR were significantly increased after BMP-2 over-expression, or significantly decreased after BMP-2 knockdown (all P < 0.05). These results reveal that BMP-2 can enhance HUVEC proliferation, migration and angiogenesis through P38, ERK and Akt/m-TOR pathway.
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Wei-Han
authors.initials: WH
authors.lastname: Zuo
authors.affiliation: Department of emergency, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Department of burns, the first Affiliated Hospital, Nanchang University, Nanchang 330006, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: An
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases