Abstract 3631: AN019, a potent anticancer agent, suppresses tumors, ErbB-2, and angiogenesis in pancreatic cancer cells

Abstract

Abstract Epidermal growth factor receptor (EGFR), a member of the HER family of receptor tyrosine kinases, has been identified as a therapeutic target for pancreatic cancer. Excessive ErbB-2 signaling is associated with the development of a wide variety of solid malignancies. In this study, we used the pancreatic cancer cell lines MIA PaCa-2 and PANC-1 to demonstrate the suppressive, anti-angiogenic, and anti-proliferative effects of a novel compound known as AN019. Here, we show that AN019 inhibits the invasiveness of pancreatic cancer cells in a dose-dependent manner and is superior to treatment with Gemcitabine alone. Angiogenic assays demonstrated that AN019 treatment retarded the invasive potential of pancreatic cancer cells and provided greater angiogenic inhibition than Gemcitabine. In addition, western blot analysis demonstrated that AN019 inhibits expression of ErbB-2 in a dose-dependent manner in MIA PaCa-2 and PANC-1 cells. In contrast, Gemcitabine lacked a similar dose response. Finally, the proliferation assay showed that while AN019 retarded proliferation in a dose-dependent manner, Gemcitabine did not. Our in vivo studies showed that expression of ErbB-2 and VEGF decreased in a dose-dependent manner in AN019-treated animals with subcutaneously implanted MIA PaCa-2 tumors. A treatment combination of AN019 and Gemcitabine had an effect similar to that of treatment with AN019 alone, thereby indicating no specific contribution from Gemcitabine. Our results demonstrate AN019 is superior to Gemcitabine, and AN019 is a specific suppressor of ErBB-2 in vitro and in vivo. In addition, AN019 has anti-proliferative and anti-angiogenic properties. Taken together, these results clearly indicate the potential therapeutic use of AN019 as an anti-cancer agent. 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 3631.