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Title: Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library

Highlights: • A specific aFGF-binding peptide AP8 was identified from a phage display library. • AP8 could inhibit aFGF-stimulated cell proliferation in a dose-dependent manner. • AP8 arrested the cell cycle at the G0/G1 phase by suppressing Cyclin D1. • AP8 could block the activation of Erk1/2 and Akt kinase. • AP8 counteracted proliferation and cell cycle via influencing PA2G4 and PCNA. - Abstract: It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blockedmore » the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.« less
Authors:
;  [1] ;  [2] ;  [1] ; ;  [3] ;  [1] ;  [3] ;  [1] ;  [3] ;  [1]
  1. College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China)
  2. Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong (China)
  3. Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China)
Publication Date:
OSTI Identifier:
22416319
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 445; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; AMINO ACIDS; BACTERIOPHAGES; CELL CYCLE; CELL PROLIFERATION; DOSES; DRUGS; FIBROBLASTS; FUNCTIONAL ANALYSIS; GROWTH FACTORS; MAMMARY GLANDS; NEOPLASMS; PEPTIDES; RECEPTORS; THERAPY