title: Endostar inhibits hypoxia-induced cell proliferation and migration via the hypoxia-inducible factor-1α/vascular endothelial growth factor pathway in vitro.
abstract: Endostar, a recombinant human endostatin, is recognized as one of the most effective angiogenesis inhibitors. The angiogenesis inhibitory effects of Endostar suggest a possible beneficial role of Endostar in choroidal neovascularization (CNV), which is predominantly induced by hypoxia. In our previous study, it was reported that Endostar may inhibit the proliferation and migration of RF/6A choroid‑retinal endothelial cells. However, the inhibitory effect of Endostar on hypoxia‑induced cell proliferation and migration in RF/6A cells has not yet been elucidated. Therefore, the present study investigated the effect of Endostar on hypoxia‑induced cell proliferation and migration in RF/6A cells and the possible mechanisms underlying this effect. Under chemical hypoxia conditions, cell viability was increased to 114.9±10.1 and 123.6±9.6% in cells treated with 100 and 200 µm CoCl2, respectively, compared with the control (P<0.01). Pretreatment with 10‑100 µg/ml Endostar significantly inhibited CoCl2‑induced cell proliferation (P<0.05), and pre‑treatment with 10 µg/ml Endostar for 24, 48 and 96 h attenuated CoCl2‑promoted cell migration by 60.5, 48.3 and 39.6%, respectively, compared with the control (P<0.001). In addition, pretreatment with 10 µg/ml Endostar reversed the cell cycle arrest at S phase and the increased expression of hypoxia‑inducible factor‑1α (HIF‑1α) and vascular endothelial growth factor (VEGF) mRNA in RF/6A cells treated with 200 µM CoCl2. These data indicate that Endostar inhibited CoCl2‑induced hypoxic proliferation and migration, and limited cell cycle progression in vitro possibly through the HIF‑1α/VEGF pathway.
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital (Binjiang Branch), School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Kana
authors.initials: K
authors.lastname: Lin
authors.affiliation: Eye Center, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ye
authors.affiliation: Eye Center, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Eye Center, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Fengying
authors.initials: F
authors.lastname: He
authors.affiliation: Eye Center, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D043169:Endostatins / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D043169:Endostatins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C522911:endostar protein