Pu Kefeng, Yuan Lihua, Chen Lisha, Wang Anxin, Zhou Xuan, Zhang Hailu, Zhu Yimin
398 Ruoshui Road, Suzhou Industrial Park, Suzhou 215123, China.
Curr Cancer Drug Targets. 2015;15(2):158-70. doi: 10.2174/156800961502150320112339.
The signal transduction pathway initiated by vascular endothelial growth factor-vascular endothelial growth factor receptor 2 (VEGF-VEGFR2) plays an important role in the angiogenesis of tumors. The effective antagonists of VEGFR2 would behave as potent drugs for the treatment of malignant cancers. In our study, specific binding peptides with high affinity to VEGFR2 were obtained through bacterial display technology. Conserved motif (FF/YEXWGVK) among those peptide sequences was discovered. One of the selected peptides, VRBP1 (YDGNSFYEMWGVKPASES) was identified by screening the biased bacterial peptide library and its physiochemical feature was further characterized. The results of surface plasmon resonance (SPR) assay indicated that the dissociation constant (KD) value of VRBP1 was 228.3 nM and this peptide competed with VEGF binding to VEGFR2. Particles conjugated with VRBP1 could recognize the human umbilical vein endothelial cells (HUVEC) which express VEGFR2 on the surface. Further therapeutic effect of VRBP1 was examined by in vivo experiments. VRBP1 could result in a significant decrease in tumor size of H460 xenografts. The results from the immunohistochemical assay showed that CD31 positive signals in VRBP1-treated group were fewer than those in the control ones. These data highlighted the potential of VEGFR2-binding peptides as effective molecules for cancer diagnosis and therapy.
由血管内皮生长因子-血管内皮生长因子受体2（VEGF-VEGFR2）启动的信号转导通路在肿瘤血管生成中起重要作用。VEGFR2的有效拮抗剂有望成为治疗恶性肿瘤的有效药物。在我们的研究中，通过细菌展示技术获得了与VEGFR2具有高亲和力的特异性结合肽。在这些肽序列中发现了保守基序（FF/YEXWGVK）。通过筛选偏向性细菌肽库鉴定出其中一个选定的肽VRBP1（YDGNSFYEMWGVKPASES），并进一步表征了其理化特性。表面等离子体共振（SPR）分析结果表明，VRBP1的解离常数（KD）值为228.3 nM，且该肽与VEGF竞争结合VEGFR2。与VRBP1偶联的颗粒能够识别表面表达VEGFR2的人脐静脉内皮细胞（HUVEC）。通过体内实验检测了VRBP1的进一步治疗效果。VRBP1可导致H460异种移植瘤的肿瘤大小显著减小。免疫组织化学分析结果显示，VRBP1治疗组的CD31阳性信号少于对照组。这些数据突出了VEGFR2结合肽作为癌症诊断和治疗有效分子的潜力。
