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Inhibition of angiogenesis has been focused on as a strategy for treating several diseases including cancer. In this study, a novel model peptide αAL14 was synthesized and used to identify its inhibitory effects on angiogenesis. The anti-angiogenic effects of αAL14 were investigated using vascular endothelial cells, HUVECs. αAL14 inhibited critical angiogenic processes including tubule formation, cell migration and cell invasion with no influence on cell proliferation in HUVECs. Activity of VEGFR2 was inhibited by αAL14 treatment in HUVECs. Additionally, activities of major subsequent downstream factors of VEGFR2 such as ERK, FAK and Akt were decreased. αAL14 affected expression of Rac1, Cdc42, Arp2 and WAVE2 which are involved in formation of lamellipodia. Moreover, αAL14 reduced NF-κB that can promote expression of several genes relating to cell invasion such as MMP2 and MMP9. Therefore, the results suggest that αAL14 has a potential to be developed as anti-angiogenic drug for treating diseases driven by abnormal angiogenesis.

The novel model peptide, αAL14, regulates angiogenesis by inhibiting VEGFR 2-mediated signaling in HUVECs