title: Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library.
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 blocked 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.
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Xiaoyong
authors: X
authors: Dai
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Cuizan
authors: C
authors: Cai
authors: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Fei
authors: F
authors: Xiao
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Yaoling
authors: Y
authors: Xiong
authors: Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Yadong
authors: Y
authors: Huang
authors: Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Qihao
authors: Q
authors: Zhang
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Qi
authors: Q
authors: Xiang
authors: Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Guofeng
authors: G
authors: Lou
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
authors: Mengyang
authors: M
authors: Lian
authors: Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong, PR China. Electronic address: tjnuszj@jnu.edu.cn.
authors: Zhijian
authors: Z
authors: Su
authors: College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China. Electronic address: tzhengq@jnu.edu.cn.
authors: Qing
authors: Q
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C101633:PA2G4 protein, human; D019151:Peptide Library; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D016601:RNA-Binding Proteins; D016220:Fibroblast Growth Factor 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Acidic fibroblast growth factor; Breast cancer; Cell cycle; Phage display; Proliferation