Inhibition of tumor growth by a peptide fusion protein binding to vascular endothelial growth factor receptor Flt-1

目的检测从十二肽库中筛选获得的能与血管内皮细胞生长因子(VEGF)受体Flt-1结合的小肽的生物学活性.方法免疫细胞化学方法检测小肽融合蛋白DHFR-F56/F90与人脐静脉内皮细胞的结合活性;鸡胚尿囊膜血管增生抑制实验检测DHFR-F56/F90能否抑制鸡胚新生血管形成;裸鼠成瘤实验检测DHFR-F56/F90对荷瘤裸鼠中肿瘤的生长抑制;免疫组织化学方法检测DHFR-F56/F90能否定位于肿瘤组织.结果小肽融合蛋白DHFR-F56/F90能与人脐静脉内皮细胞结合,DHFR-F56能抑制鸡胚尿囊膜新生血管的形成,且DHFR-F56能与肿瘤细胞结合,促进肿瘤组织坏死及显著抑制肿瘤生长.结论十二肽F56是VEGF结合Flt-1的有效拮抗剂,具有抑制VEGF诱导的新生血管形成而抗肿瘤生长和转移的潜在应用前景.Investigating the bio-activities of peptides selected from phage display peptide library with vascular endothelial growth factor receptor Flt-1.Activities of DHFR-F56/F90 binding to human ubilial vein endothelial cells were detected by immunocytochemistry, and the activity of antiangiogenesis was determined with chick embryo chorioallantoric membrane (CAM) assay. Balb/c nude mice were used as model to detect the activity of DHFR-F56/F90 on inhibiting tumor growth, and immunohistochemistry was employed to determine the localization of the DHFR-F56/F90 in tumor.DHFR-F56/F90 can bind to HUVEC, and DHFR-F56 inhibite angiogenesis in CAM. Meanwhile DHFR-F56 can bind with tumor cells, induce tumor necrosis and inhibit tumor growth in vivo.The peptide F56 is an effective antagonist of VEGF binding to Flt-1 and has a potent utility in antiangiogenesis and inhibiting tumor growth.国家自然科学基金; 国家高技术研究发展计划(863计划); 北京市科委科研项目PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)0191342-13458