Abstract 5206: VEGF-A/VEGFR-2 signaling might be a promising target for the tumor invasion of pancreatic cancer

Abstract

Abstract Introduction: Pancreatic cancer is one of the most lethal solid tumors. Vascular endothelial growth factor receptors (VEGFRs) are expressed not only by endothelial cells but also by some types of cancer cells, including pancreatic cancer cells. VEGFRs might play an important role for the development of cancer cells. The purpose of this study was to evaluate the efficacy of VEGF/VEGFR-2 targeted therapy in pancreatic carcinoma. We here demonstrated that VEGFR-2 signaling on pancreatic cancer cells might be a promising therapeutic target for the invasion of pancreatic cancer. Materials & Methods: Three pancreatic carcinoma cell lines, MiaPaCa-2, OCUP-AT and Panc-1, were used. The effect of anti-VEGF antibody, bevacitumab, a tyrosine kinase inhibitor against VEGFRs, sunitinib, and VEGF-R2 siRNA on cancer invasion was examined by invasion assay. The expression level of VEGFR mRNA of cancer cells was examined by RT-PCR. The effect of VEGF, bevacitumab and sunitinib on MAPK and PI3K signaling pathway was examined. Result: VEGF-A significantly increased the number of migration cells of MiaPaCa-2 and OCUP-AT, but not that of Panc-1. Bevacitumab and sunitinib significantly decreased the migration ability of MiaPaCa-2 and OCUP-AT cells. The expression levels of VEGF-R2 were high in MiaPaCa-2 and OCUP-AT cells, in compared with Panc-1 cells. Invasion and migration ability of MiaPaCa-2 cells significantly (p<0.05) decreased by VEGFR-2 siRNA treatment. The level of VEGFR-2 autophosphorylation, p-ERK and p-Akt expression was increased by VEGF-A, and decreased by bevacitumab and sunitinib. Conclusion: The invasion of pancreatic cancer cells was closely associated with VEGF-A/VEGFR-2 signaling. VEGF-A/VEGFR-2 inhibition by bevacitumab or sunitinib appears therapeutically promising in pancreatic cancer with VEGFR-2 expression. 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 5206.