Current treatment options for localized CaP are radiation therapy, surgery and endocrine therapy. Although aggressive radiation does improve biochemical control, greater rectal and urinary toxicities also occurred. Local failure after RT remains 20%�C35% in intermediate- and high-risk CaP patients, leading to increased metastasis and lower survival. Thus, investigation of a novel combination approach with a selective radio-sensitizer with RT to enhance CaP radiosensitivity is MK-1775 distributor urgently needed. Histone deacetylase inhibitors are an emerging group of agents which targets histone deacetylase and promising radiosensitizers currently under investigation. Radiosensitization by HDACi, such as valproic acid has been demonstrated in preclinical studies. HDACi is a potent inducer or regulator of cellular behaviours such as apoptosis, cell cycle and DNA repair processes. It is believed to exert its effects mainly by modifying histone and chromatin structures, thus modulate gene transcription. Moreover, these acetylases and deacetylases can also modulate cell functions independent of gene expression by acting on non-histone proteins such as p21, p53, Ku70. Through acting on a series of histone and non-histone proteins, HDACi is capable of mediating apoptosis, cell cycle, and DNA repair processes in a well orchestrated manner. LBH589 is a hydroxamic acid derivative and a novel pan- HDACi. Qian et al. reported that LBH589 alone reduced angiogenesis and tumor growth in a PC-3 xenograft animal model. A phase I study has been conducted by treating castration-resistant prostate cancer patients using oral LBH589 with or without docetaxel, demonstrating promising results for future clinical application. These results support the hypothesis that LBH589 may be (+)-JQ1 useful in combination with RT for treating localized CaP. In this study, we hypothesized that LBH589 could kill CaP cells and treatment of CaP cells with LBH589 before RT would increase the sensitivity of CaP cells to RT. Since persistent DNA DSB were seen in combination-treated cells, two NHEJ pathway proteins which are responsible for repair of RT-induced DSB were further examined by western blotting in RT- and combination-treated cells. Expression patterns of Ku70 and Ku80 were different for PC-3 and LNCaP cells. In PC-3 cells, positive expression of Ku70 and Ku80 was found 6 h after RT and increased gradually until 72 h after RT whereas expression of Ku70 and Ku80 was undetectable after 48 h in combination treatment.