title: Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.
abstract: Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Ti Yuan Bei, Huan-Hu-Xi Road, He-Xi District, Tianjin 300060, China.
authors.forename: Shuang-Xia
authors.initials: SX
authors.lastname: Zhang
authors.forename: Cong
authors.initials: C
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Xing-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiong-Zhi
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D056945:Hep G2 Cells; D006493:Heparin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D020349:Surface Plasmon Resonance; D023041:Xenograft Model Antitumor Assays; D000099175:Heparanase
chemical_list: D004365:Drugs, Chinese Herbal; D051766:Early Growth Response Protein 1; D016222:Fibroblast Growth Factor 2; D005966:Glucuronidase; D006493:Heparin; D011134:Polysaccharides; D000099175:Heparanase; C519079:gepsin