Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer

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• 作者：Wenhui Wang^a ; Xilei Chen^a ; Tao Li^a ; Yanmei Li^a ; Ruixue Wang^a ; Dan He^a ; Wu Luo^a ; Xiaokun Li^a ; ^b ; Xiaoping Wu^a ; ^b ; ^{twxp@jnu.edu.cn}
• 关键词：Fibroblast growth factor 8b ; Phage display ; Proliferation ; Cell cycle ; Prostate cancer
• 刊名：Experimental Cell Research
• 出版年：2013
• 出版时间：1 May, 2013
• 年：2013
• 卷：319
• 期：8
• 页码：1156-1164
• 全文大小：948 K

文摘

Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163-169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163-169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer.