https://scholars.lib.ntu.edu.tw/handle/123456789/564172
標題: | Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective alphav/ beta 3 blockade of endothelial cells | 作者: | Yeh C.-H. Peng H.-C. RONG-SEN YANG TUR-FU HUANG |
公開日期: | 2001 | 卷: | 59 | 期: | 5 | 起(迄)頁: | 1333-1342 | 來源出版物: | Molecular Pharmacology | 摘要: | Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, although angiogenic factor and integrin-extracellular matrix interaction modulate this process. We report here that a snake venom-derived disintegrin, rhodostomin, inhibited distinct steps in angiogenesis elicited by basic fibroblast growth factor (bFGF), and also suppressed in vivo murine melanoma tumor growth. Rhodostomin dose-dependently inhibited bFGF-induced human umbilical vein endothelial cell (HUVEC) proliferation as examined by cell number count, metabolic activity, and BrdU incorporation assays with submicromolar IC50 values. However, it apparently did not affect the viability of murine B16F10 melanoma cells, even up to 50 μM. Rhodostomin also inhibited HUVEC migration and invasion evoked by bFGF, and tube formation of bFGF-treated HUVECs in Matrigel. Moreover, rhodostomin selectively inhibited bFGF-, but not vascular endothelial growth factor-associated angiogenesis in the chick chorioallantoic membrane model. Furthermore, rhodostomin blocked both bFGF- and B16F10-induced neovascularization in murine Matrigel plug model and suppressed the growth of subcutaneously inoculated B16F10 solid tumor, leading to a prolonged survival of the rhodostomin-treated C57BL/6 mice. The antiangiogenic effect of rhodostomin on bFGF-treated HUVECs is related to the integrin αvβ3 blockade, as evidenced by its selective inhibition on the binding of 7E3, a monoclonal antibody (mAb) raised against αvβ3, but not that of P1F6, an αvβ3 mAb toward both naive and bFGF-primed HUVECs. Moreover, 7E3 specifically blocked fluorescein isothiocyanate-conjugated rhodostomin binding to HUVEC, whereas P1F6 and anti-integrin α2, α3, α4, or α5 mAbs did not. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564172 | ISSN: | 0026895X | DOI: | 10.1124/mol.59.5.1333 | SDG/關鍵字: | basic fibroblast growth factor; disintegrin; eptifibatide; fluorescein isothiocyanate; monoclonal antibody; rhodostomin; snake venom; unclassified drug; angiogenesis; animal cell; animal experiment; animal model; article; cancer inhibition; cell count; cell invasion; cell metabolism; cell migration; cell proliferation; controlled study; dose response; drug effect; drug inhibition; drug mechanism; endothelium cell; human; human cell; IC 50; male; mouse; nonhuman; priority journal; tumor vascularization |
顯示於: | 藥理學科所 |
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