Abstract 4813: Magnetic iron oxide nanoparticles enhance anti-tumor effect of docetaxel on prostate cancer cells via ROS generation and NF-kappa B signaling

Abstract

Abstract Chemotherapy is one of treatment options for castration-resistant prostate cancer. Especially, docetaxel-based chemotherapy has been shown to improve the quality of life in patients with the advanced disease. However, this needs to be improved because of limitations by lack of specificity, toxicity, and progression of docetaxel-resistance. Thus, combination of docetaxel with other compounds or drugs is needed to overcome these problems. Magnetic iron oxide nanoparticles (MgNPs, Fe3O4) have been investigated for nanomedicine such as drug delivery, cancer diagnosis and therapy. We have also shown that MgNPs would modify the effect of chemotherapy in prostate cancer cells in vitro. The purpose of this study was to analyze the combined effect of docetaxel and non-/carboxyl-modified magnetic nanoparticles (MgNPs/MgNPs-COOH) on a prostate cancer cell line, DU145 and clarify their mechanisms. While only MgNPs produced reactive oxygen species (ROS) and 8-OHdG, MgNPs-COOH did neither produce ROS nor 8-OHdG. The combination of docetaxel and MgNPs-COOH more effectively inhibited cancer cell growth and induced apoptosis compared with combination of docetaxel and MgNPs. Although docetaxel induced NF-kappa B expression, combination of docetaxel and MgNPs inhibited NF-kappa B expression compared with combination of MgNPs-COOH and docetaxel. However, both combinations increased p-Akt expression. These results suggest that MgNPs/MgNPs-COOH may enhance effect of docetaxel on prostate cancer cells via NF-kappa B signaling, however different factors may be involved in these phenomena, leading to new tumor ablation therapies. Citation Format: Kanako Kojima, Saho Hashimoto, Rina Sakamaki, Sanai Takahashi, Risa Kasakura, Ryo Maruyama, Tadashi Nittami, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Magnetic iron oxide nanoparticles enhance anti-tumor effect of docetaxel on prostate cancer cells via ROS generation and NF-kappa B signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4813.