Lin K.-T.Lien J.-C.Chung C.-H.Kuo S.-C.TUR-FU HUANG2021-05-312021-05-312012281298https://scholars.lib.ntu.edu.tw/handle/123456789/564124Angiogenesis plays a critical role in many physiological and pathological phenomena. A number of anti-angiogenesis drugs have been used in the clinical treatment of diseases such as malignant tumors and macular degeneration. Vascular endothelial growth factor (VEGF), the major pro-angiogenesis factor, is known to stimulate various steps of endothelial angiogenic activity, such as proliferation, migration, and differentiation into vessel-like tubes. In this study, we tested the effects of bp5250 on the angiogenesis of human umbilical endothelial cells (HUVECs). Bp5250 suppressed VEGF-induced endothelial cell proliferation by triggering apoptosis, and reduced endothelial cell migration toward VEGF. Bp5250 also decreased VEGF-stimulated tube formation and rat aortic ring sprouting on Matrigel in a concentration-dependent manner. In the VEGF-activated signaling pathways, bp5250 decreased the phosphorylation of ERK, p38, PI3K-AKT, Src, and FAK and also reduced the activation of the cytoskeleton-associated Rho family, all in a concentration-dependent manner. Bp5250 also attenuated the hypoxia-inducible factor-1α (HIF-1α) and VEGF-stimulated mRNA expression of HUVECs under the hypoxic condition. In vivo, angiogenesis was restrained by a daily intraperitoneal administration of bp5250 in a dose-dependent manner (1-3 mg/kg/d) in the Matrigel plug implantation assay. These results indicate that bp5250 is a potential candidate for developing anti-angiogenic agents. ? 2011 Springer-Verlag.[SDGs]SDG2[SDGs]SDG3angiogenesis inhibitor; bp 5250; mitogen activated protein kinase p38; protein kinase B; protein kinase p60; unclassified drug; vasculotropin; angiogenesis; animal experiment; animal tissue; antiangiogenic activity; apoptosis; article; cell migration; cell proliferation; controlled study; endothelium cell; enzyme phosphorylation; human; human cell; nonhuman; protein expression; rat; signal transduction; umbilical vein endothelial cell; Angiogenesis Inhibitors; Animals; Anoxia; Aorta; Apoptosis; Cell Movement; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Pyrazoles; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vascular Endothelial Growth Factor Ajournal article10.1007/s00210-011-0690-2219472522-s2.0-84857034739