A novel FGF2 antagonist peptide P8 with potent antiproliferation activity
Some fibroblast growth factors (FGFs) play a critical role in tumorigenesis and progression. Among them, FGF2 was highly expressed in some tumors, and antagonists binding to FGF2 can suppress the growth of tumor cells. Therefore, FGF2 has been considered as an important target in cancer therapy. In this study, we identified a novel FGF2-binding short peptide (P8, PLLQATAGGGS-NH2) using phage display technology and alanine scanning. The P8 peptide suppressed FGF2-induced proliferation with no cytotoxic effect on cells, arrested the cycle at the G0/G1 phase in B16-F10 cells, and downregulated the activation of fibroblast growth factor receptor substrate 2α (FRS2α)/ERK cascade in B16-F10, NIH-H460, and SGC-7901 cells. Besides, P8 peptide can also inhibit the phosphorylation of FRS2α stimulated by FGF1 and KGF2. These implied that P8 peptide may develop as a multi-target antagonist peptide contributing to tumor treatment.
KeywordsFGF2-binding peptide Cell proliferation Cell cycle Signaling pathway Multi-targets
This work was supported by grants from the National Natural Science Foundation of China (81102310, 81272462, 81101712), the Natural Science Foundation of Zhejiang Province of China (Y4110029), Technology Foundation for Medical Science of Zhejiang Province (2012KYA127), the Fundamental Research Funds for the Central Universities (X. Wu), Guangdong Provincial “Thousand-Hundred-Ten Talent Project” (X. Wu), Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, and National Undergraduate Training Programs for Innovation and Entrepreneurship (201310343001).
Conflicts of interest
- 13.Takano S, Gately S, Neville ME, Herblin WF, Gross JL, Engelhard H, et al. Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator. Cancer Res. 1994;54:2654–60.PubMedGoogle Scholar
- 16.Wu J, Liang G, Wu X, Yang S, Li X. Progress of inhibitors targeting fibroblast growth factor. Chem Online. 2010;73:140–6.Google Scholar
- 18.Fan H, Zhou H, Li W. The interaction of fibroblast growth factor/fibroblast growth factor receptor and FGF inhibitors. Prog Biochem Biophys. 2001;28:338–41.Google Scholar