title: Cornin induces angiogenesis through PI3K-Akt-eNOS-VEGF signaling pathway.
abstract: In the present study, we sought to elucidate whether Cornin contributes to induce angiogenesis and its mechanisms. To this end, we examined the role of Cornin on human brain microvascular endothelial cell line (HBMEC) proliferation, invasion, and tube formation in in vitro. For study of mechanism, the phosphoinositide 3 kinase (PI3K)-Akt inhibitor LY294002, endothelial nitric oxide synthase (eNOS) inhibitor L-NAME, vascular endothelial growth factor (VEGF) antagonist sFlt-1 and VEGF receptor blocker SU-1498 were used. HMBEC proliferation was tested by MTT. Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. PI3K-Akt-eNOS-VEGF pathway activation in HMBEC was tested by Western blot. Our data suggested that Cornin induces angiogenesis in vitro by increasing proliferation, invasion and tube formation. VEGF expression was increasing by Cornin and counteracted by VEGF antagonist sFlt-1, LY294002 and L-NAME in HMBEC. Tube formation was increased by Cornin and counteracted by VEGF receptor blocker-SU1498, LY294002 and L-NAME. It may be suggested that Cornin induces angiogenesis in vitro via a programmed PI3K/Akt/eNOS/VEGF signaling axis.
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
authors.forename: Zechun
authors.initials: Z
authors.lastname: Kang
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Luan
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D057889:Iridoid Glycosides / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D057889:Iridoid Glycosides; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C000511:cornin iridoid; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Angiogenesis; Cornin; HBMEC; VEGF; eNOS