title: Perifosine as potential anti-cancer agent inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells.
abstract: Targeting angiogenesis is considered an effective strategy for treating the expansion and metastasis of tumors. The aim of this study is to assess the effects of perifosine, an inhibitor of Akt, on cell proliferation, apoptosis, angiogenesis, and VEGF-induced cell migration in cultured human umbilical vein endothelial cells (HUVECs) in vitro. MTT and cell cycle analysis results indicated that perifosine inhibited the growth of HUVECs in a dose-dependent manner, arrested cell cycle progression at the G(2) phase with regulation the expression of p21 and cyclinB1. Apoptosis induced by the higher concentrations of perifosine in HUVECs was also observed. In addition, tube formation of HUVECs and VEGF-induced cell migration were markedly inhibited by perifosine. Western blotting analysis of cell signaling molecules indicated that perifosine inhibited ERK and p38 phosphorylation in HUVECs. These results suggest that perifosine exerts anti-angiogenic activity in HUVECs and is a promising agent for treatment of angiogenesis related-diseases.
authors.affiliation: School of Biological Science, Taishan Medical University, Taian 271016, People's Republic of China. fengzewang@gmail.com
authors.forename: Feng Ze
authors.initials: FZ
authors.lastname: Wang
authors.forename: Hong Rong
authors.initials: HR
authors.lastname: Fei
authors.forename: Xiao Qian
authors.initials: XQ
authors.lastname: Li
authors.forename: Renjiu
authors.initials: R
authors.lastname: Shi
authors.forename: De Cai
authors.initials: de C
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D056744:Cyclin B1 / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D056744:Cyclin B1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D010767:Phosphorylcholine; C105905:perifosine; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases