title: Fibrinogen-derived fibrinostatin inhibits tumor growth through anti-angiogenesis.
abstract: Angiogenesis is a prerequisite of tumor growth and metastasis and, thus, anti-angiogenesis treatment has become an important part of cancer therapy. A 15-amino acid peptide of the fibrinogen α chain, fibrinostatin, was previously found in serum samples of gastric cancer patients. Herein we demonstrated that fibrinostatin has anti-angiogenesis activity in several angiogenesis models and it reduces tumor growth in mouse xenografts and allografts. Increased tumor necrosis and reduced microvessel density in tumors were observed in mouse xenograft models. Fibrinostatin inhibited proliferation and induced apoptosis in HUVEC, but not in cancer cells. In addition, fibrinostatin specifically entered HUVEC. Fibrinostatin also prevented migration, adhesion and tubule formation of HUVEC in vitro. A single-dose acute toxicity testing and a repeated-dose chronic toxicity study in the mouse, rat and monkey indicated that fibrinostatin had a wide margin of safety. Taken together, fibrinostatin shows promise as a potential anti-angiogenesis therapeutic agent.
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Chuanke
authors: C
authors: Zhao
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Yahui
authors: Y
authors: Su
authors: Thoracic Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Jianzhi
authors: J
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Qin
authors: Q
authors: Feng
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Like
authors: L
authors: Qu
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Lixin
authors: L
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Caiyun
authors: C
authors: Liu
authors: Minimally Invasive Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors: Beihai
authors: B
authors: Jiang
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Lin
authors: L
authors: Meng
authors: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Chengchao
authors: C
authors: Shou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002642:Chick Embryo; D005340:Fibrinogen / Q000494:pharmacology*; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D010455:Peptides; D005340:Fibrinogen
keywords: Anti-angiogenesis; fibrinogen; fibrinostatin; peptide; tumor inhibition