arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells三氧化二砷增强androgen-dependent的辐射敏感性和独立的人类前列腺癌细胞.pdfVIP

Arsenic Trioxide Enhances the Radiation Sensitivity of Androgen-Dependent and -Independent Human Prostate Cancer Cells 1 1 2 1 Hui-Wen Chiu , Yi-An Chen , Sheng-Yow Ho , Ying-Jan Wang * 1 Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan, 2 Sinlau Christian Hospital, Tainan, Taiwan Abstract Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen-independent human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS) generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen- independent prostate cancer. Citation: Chiu H-W, Chen Y-A, Ho S-Y, Wang Y-J (2012) Arsenic Trioxide Enhances the Radiatio