Research Papers:
Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
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Abstract
Xiaoping Wu1,2,*, Huixian Huang3,*, Cong Wang1,2,*, Shaoqiang Lin1, Yadong Huang3, Yi Wang1, Guang Liang1, Qiuxia Yan3, Jian Xiao1, Jianzhang Wu1, Yongguang Yang4, Xiaokun Li1,3
1 School of Pharmaceutical Science, Key Laboratory of Biotechnology and Pharmaceutical Engineering of Zhejiang Province, Wenzhou Medical College, Wenzhou, PR China;
2 Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, PR China;
3 National Engineering Research Center for Gene Medicine, Jinan University, Guangzhou, PR China; and
4 Columbia Center for Translational Immunology, Columbia University Medical Center, New York, USA
* These authors contributed equally to this paper.
Correspondence:
Xiaoping Wu, email:
Correspondence:
Yongguang Yang, email:
Correspondence:
Xiaokun Li, email:
Keywords: bFGF, phage display, proliferation, cancer therapy
Received: August 21, 2013 Accepted: September 29, 2013 Published: October 1, 2013
Abstract
Basic fibroblast growth factor (bFGF) has been implicated in tumor growth via interactions with its receptors (FGFRs) on the cell surface and therefore, bFGF/FGFRs are considered essential targets for cancer therapy. Herein, a consensus heptapeptide (LSPPRYP) was identified for the first time from a phage display heptapeptide library after three sequential rounds of biopanning against FGFR-expressing cells with competitive displacement of phage by bFGF, followed by subtraction of non-specific binding by FGFR-deficient cells. Phage bearing LSPPRYP showed high levels of binding to Balb/c 3T3 cells expressing high-affinity bFGF-binding FGFR (bFGFR), but not to the cells that do not express bFGFR (Cos-7), or express a very low affinity bFGFR (HaCat). The selected-phage-derived peptide synthesized by solid phase method using a rapid and practical Fmoc strategy was found to specifically compete with bFGF for binding to its receptors, inhibit bFGF-stimulated cell proliferation by inducing cell cycle arrest, and block bFGF-induced activation of Erk1 and Erk2 kinase in B16-F10 melanoma cells. Importantly, treatment of melanoma-bearing mice with the synthetic peptide significantly suppressed tumor growth. The results demonstrate a strong anticancer activity of the isolated bFGFR-binding peptide (and its future derivatives), which may have great potential for cancer therapy.
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