Abstract 1368: L-5F, an ApoA-I mimetic peptide, inhibits tumor angiogenesis by suppressing VEGF/bFGF signaling pathways

Abstract

Abstract Objective We recently demonstrated that overexpression of ApoA-I inhibits tumor growth and improves survival in mice. In the present study we examined whether apoA-I mimetic peptide, L-5F reduces tumor development in mice by inhibiting angiogenesis. Methods Flank tumors were generated in immunocompetent C57BL6/J mice as described previously (Zhang L, et al. 2002) by injecting ID8 cells, a mouse ovarian cancer cell line. L-5F was injected s.c. once a day for 5 weeks (10 mg/kg). 3D vessel images of tumor tissues were created using a micro-CT scanner from Numira Biosciences. The effects of L-5F in vitro were studied in human umbilical vascular endothelial cells (HUVEC) following VEGF and bFGF treatment. MTS assay, BrdU cell proliferation assay, wound-healing assay, and trans-well assay were used to determine cell viability, proliferation, migration, and invasion of HUVEC, respectively. Activation of Erk and Akt pathways were analyzed using western blots. Results Daily s.c. injection of L-5F significantly reduced tumor size and quantity and size of vessels of flank tumors in C57BL6/J mice, compared to mice that did not receive L-5F peptide. L-5F (10 µg/ml) significantly inhibited both VEGF- and bFGF-induced cell viability (∼46% for VEGF and ∼56% for bFGF), proliferation (∼50% for VEGF and ∼70% for bFGF), migration (∼80% for VEGF and ∼77% for bFGF), and invasion (∼65% for VEGF and ∼44% for bFGF) in HUVECs. L-5F mediated effects were dose-dependent between 1 and 10 µg/ml including the inhibition VEGF and bFGF-induced phosphorylation of Erk and Akt. L-5F did not affect the viability and proliferation of HUVECs in the basal state (i.e. absence of VEGF and bFGF treatments). Conclusion Our data suggest that apoA-I mimetic peptide, L-5F inhibits tumor development in mice, in part, by inhibiting angiogenesis. ApoA-I mimetic peptides may serve as novel anti-angiogenesis and anticancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1368.