Fibrinogen‐derived fibrinostatin inhibits tumor growth through anti‐angiogenesis

Cancer Science

Chuanke Zhao¹  Yahui Su¹  Jianzhi Zhang³  Qin Feng¹  Like Qu¹  Lixin Wang¹  Caiyun Liu¹  Beihai Jiang²  Lin Meng¹ 

[1] Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China;Minimally Invasive Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China;Thoracic Surgery, Peking University Cancer Hospital and Institute, Beijing, China

关键词: Anti‐angiogenesis;    fibrinogen;    fibrinostatin;    peptide;    tumor inhibition;   

DOI  :  10.1111/cas.12797

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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