It was reported that only ~10% of DSB were repaired by the HR pathway in mammalian cells. In the current study, we have shown that the BRCA1, BRCA2 and Rad51 proteins which are the main partakers in the HR pathway, were presented with the delayed increase in the combination treatment group, when compared to RT alone group. Therefore, these HR repair pathway proteins are involved in the radiosensitization effect induced by LBH589. Given that LBH589 is a pan-HDACi, it may interfere with activation of all these proteins by increasing acetylation. This could be the possible Tubulin Acetylation Inducer reason why the DNA DSBs repair was significantly impaired in the combination-treated CaP cells. Our results are consistent with the observation by other group that most of genes involved in cell cycle control, DNA replication and DNA damage repair were downregulated after treatment with HDACi. Our findings indicate that both NHEJ and HR repair pathways are involved in DNA repair defective in the combination treatment. The loss of histone lysine acetylation has been observed to be related with carcinogenesis. Over the past decade, HDAC, which is responsible for removing the acety group from histones, have evolved as one of the major cancer targets for epigenic based therapies. Combining epigenic therapy with HDACi or traditional regimens such as chemotherapy or RT is a new developing research area in reducing BYL719 toxicity in chemotherapy and radiotherapy. Like other HDACis, the LBH589 -mediated radiosensitization might result from several mechanisms: 1) the expression of check point and DSB repair proteins were inhibited by HDACi ; 2) HDACi mediated deacetylation may cause disruption of protein�Cprotein interaction during cell cycle control and DSB repair ; 3) the HDACi treatment resolves the compact structure of the chromatin, which may lead to the susceptibility of the cells to radiation damage and the activation of specific gene transcription. All above reasons may cause the defects in DNA damage repair and checkpoint proteins which would allow the cells to proceed through the cell cycle with damaged DNA, resulting in more apoptosis. This phenomenon has been shown for cell death upon chemo- and radiotherapy treatment in several cancers. Our study indicates that LBH589, even in a low dose, is a potent radiosensitizer in CaP cells in vitro, and cell cycle check point and DSB repair proteins are activated in response to RT alone so that the cells may gain sufficient time for DNA repair. After CaP cells received the combination therapy, the activation of these proteins were inhibited, leading to DNA repair defect and the increase of radiosensitivity of CaP cells. In summary, our results demonstrated for the first time that LBH589 at low concentration sensitizes CaP cells to RT.