Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation.
Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation.
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鉴定一种可阻断碱性成纤维细胞生长因子介导的细胞增殖的新型肽
DOI：
10.18632/oncotarget.1312
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Wu X;Huang H;Wang C;Lin S;Huang Y;Wang Y;Liang G;Yan Q;Xiao J;Wu J;Yang Y;Li X
碱性成纤维细胞生长因子（bFGF）通过与细胞表面上的其受体（FGFR）相互作用而参与肿瘤生长，因此，bFGF/FGFR被认为是癌症治疗的重要靶点。在此，共有七肽（LSPPRYP）是第一次从噬菌体展示七肽库后，连续三轮的生物淘选对FGFR表达细胞与竞争性置换的噬菌体的bFGF，随后扣除非特异性结合的FGFR缺陷型细胞。携带LSPPRYP的噬菌体显示与表达高亲和力bFGF结合FGFR（bFGFR）的Balb/c 3 T3细胞的高水平结合，但不与不表达bFGFR（Cos-7）或表达极低亲和力bFGFR（HaCat）的细胞结合。固相法合成的选择性噬菌体衍生肽，使用快速和实用的Fmoc策略，发现特异性与bFGF竞争结合其受体，通过诱导细胞周期阻滞抑制bFGF刺激的细胞增殖，并阻断bFGF诱导的B16-F10黑色素瘤细胞中Erk 1和Erk 2激酶的激活。重要的是，用合成肽治疗荷黑色素瘤小鼠显著抑制了肿瘤生长。结果表明，分离的bFGFR结合肽（及其未来的衍生物）具有很强的抗癌活性，这可能对癌症治疗具有很大的潜力。
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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影响因子：
3
作者：
Korc M;Friesel RE
通讯作者：
Friesel RE
影响因子：
5.7
作者：
Tsunoda, Satoshi;Nakamura, Toshiyuki;Saiki, Ikuo
通讯作者：
Saiki, Ikuo
影响因子：
--
作者：
Posch C;Ortiz-Urda S
通讯作者：
Ortiz-Urda S
影响因子：
5.3
作者：
Wu X;Yan Q;Huang Y;Huang H;Su Z;Xiao J;Zeng Y;Wang Y;Nie C;Yang Y;Li X
通讯作者：
Li X
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
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