The effect of a tumor targeting peptide on the proliferation and migration of breast tumor cell line

Vascular endothelial growth factor (VEGF) family members and their receptors (VEGFR) are essential in the formation of new blood vessels by angiogenesis. Recent studies aimed at inhibiting angiogenesis have focused specifically on inhibiting the VEGF-R۲ receptor, and significant advances have been made in clinical trials of antagonists designed as antiangiogenic agents. In the present study, based on the VEGF-A/VEGF-R۲ structure, a cyclic peptide (VGB-A۱) was designed from the L۱ loop region containing residues ۳۳-۵۱ of VEGF-A. The ability of VGB-A۱ bound to both VEGF-R۱ and VEGF-R۲ receptors was evaluated and the bioactivity and efficacy of the peptide were evaluated in vitro. Based on immunocytochemical studies, VGB-A۱ bound to VEGF-R۲ and blocked their homo- and heterodimerization in ۴T۱ mammary carcinoma tumor cells. Peptide blocked cell migration and metastasis by inhibiting phosphorylation and thus inhibiting the activation of ERK۱/۲, AKT and further inhibiting the FAK/Paxillin, MMP and E-Cad signaling pathways in ۴T۱. VGB-A۱ can be a strong candidate for therapeutics in various angiogenesis therapies, especially cancer.

کلیدواژه ها:

VEGF-A ، KDR ، Angiogenesis ، Peptide Design