[Show abstract][Hide abstract] ABSTRACT: Although the VEGF-Flk-1-pathway has been known as the major driving force of angiogenesis, new evidence has shown that VEGFR-1/Flt-1 plays important roles during the neovascularization under pathological conditions including tumor, atherosclerosis and arthritis. In search of Flt-1 receptor antagonizing peptides, we screened a phage display 12-mer-peptide library with recombinant Flt-1 protein. Seven candidate peptides were identified that specifically bound to VEGF receptor Flt-1, of which peptide F56 (WHSDMEWWYLLG) almost abolished VEGF binding to receptor Flt-1 in vitro. In vivo, F56 fused with DHFR (DHFR-F56) inhibited angiogenesis in a CAM assay. Moreover, DHFR-F56 significantly inhibited the growth of nodules of human gastric cancer cell line MGC-803 in BALB/c nude mice. Histological analyses showed that necrosis of the implanted tumor was markedly enhanced following treatment with DHFR-F56. In the severe combined immunodeficiency disease (SCID) mouse model for studying metastasis of the human breast cancer cell line BICR-H1, synthetic peptide F56 significantly inhibited tumor growth and lung metastases. Taken together, our results have demonstrated that peptide F56, as a Flt-1 receptor antagonist, fulfilled the antiangiogenic and antimetastatic effects by specifically interfering with the interaction between VEGF and receptor Flt-1. Thus, short peptide F56 may have clinical potential in tumor therapy.
Preview · Article · Aug 2004 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2002 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) binding to its tyrosine kinase receptors (KDR/FLK1, Flt-1) induces angiogenesis.
In search of the peptides blocking VEGF binding to its receptor KDR/FLK1 to inhibit tumorangiogenesis and growth, we screened
a phage display peptide library with KDR as target protein, and some candidate peptides were isolated. In this study, we cloned
the DNA fragment coding the peptide K237 from the library, into a vector pQE42 to express fusion protein DHFR-K237 in E. coli M15. The affection of fusion protein DHFR-K237 on endothelial cell proliferation and angiogenesis was investigated. In vitro, DHFR-K237 could completely block VEGF binding to KDR and significantly inhibit the VEGF-mediated proliferation of the human
vascular endothelial cells. In vivo, DHFR-K237 inhibited angiogenesis in chick embryo chorioallantoric membrane and tumor growth in nude mice. These results
suggest that K237 is an effective antagonist of VEGF binding to KDR, and could be a potential agent for cancer biotherapy.
No preview · Article · Jan 2002 · Chinese Science Bulletin