Seal, Sudeepta

Abstract A substantial body of evidence suggests an association between vascular endothelial growth factor (VEGF) and the neovascularization that occurs with ovarian carcinogenesis. VEGF expression has been directly related to ascites accumulation. Phase II clinical trials in ovarian cancer using single-agent bevacizumab (a monoclonal antibody directed against VEGF) showed promising results, clearly highlighting the importance of anti-angiogenesis based-targeted therapies in ovarian cancer. One of the ways that VEGF mediates angiogenesis is by activating NADPH oxidase-ROS pathway. We have developed and engineered nanoparticles (NP) of cerium oxide (Nanoceria, NCe), a rare earth oxides, which have been tested for their ability to serve as free-radical scavengers to provide protection against chemical, biological, and radiological insults that promote the production of free radicals. Here we show for the first time that treatment of human umbilical vascular endothelial cells (HUVECs) with NCe resulted in inhibition of proliferation, capillary tube formation and VEGF165 induced activation of VEGFR2 and MMP2. Additionally, NCe treatment inhibited growth factor induced migration and invasion of ovarian cancer cells. Collectively, these results indicate that cerium oxide based NP could potentially be used as an antiangiogenic therapeutic agent in ovarian cancer. Citation Information: Cancer Res 2009;69(23 Suppl):C48.