title: Cytotoxic effect of a combination of bluetongue virus and radiation on prostate cancer.
abstract: This study aimed to investigate the lethal effect of the combination of bluetongue virus (BTV) and radiation on RM-1 murine prostate cancer cellsin vitroandin vivo. Various cell lines were infected with BTV and the cytotoxicity was tested by a lactate dehydrogenase (LDH) release bioassay. Additionally, the RM-1 cells were treated with radiation and/or BTV to assess cell viability using the Cell Counting Kit-8 method. The levels of apoptosis of the RM-1 cells were detected by fluorescence-activated cell sorting (FACS). To identify a possible mechanism for the radiation-induced change in the oncolytic activity of BTV, cell cycle analyses were performed. The effects of different schedules of BTV and radiotherapy on cytotoxicity were assessedin vitroand the combined effect was also assessed in tumor modelsin vivo. The results demonstrated that BTV had a selective cytotoxic effect on RM-1 and PC-3 cancer cells, but did not affect normal cells, specifically, human umbilical vein endothelial cells and smooth muscle cells. The combination of BTV and radiation enhanced the cytotoxicity compared with that of each agent alone and had a synergistic effectin vitroandin vivo. The results of the FACS confirmed that radiotherapy induced apoptosis, as did BTV alone, and the combination treatment generated the most prominent levels of apoptosis, which were the highest in the early stage. The analysis of the cell cycle indicated that the G2-M phase levels increased after irradiation followed by infection with BTV. In conclusion, the combination of BTV and radiotherapy had an enhanced cytotoxic effect on RM-1 cellsin vitroandin vivocompared with that of either treatment alone, and demonstrated a synergistic efficacy, in addition to a marked apoptosis-inducing effect. These results support the future investigation of BTV for potential clinical use in patients with prostate cancer.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Mei-Nan
authors.initials: MN
authors.lastname: Chen
authors.affiliation: Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, Hubei 435000, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhan
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, Hubei 435000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
keywords: bluetongue virus; cell apoptosis; combined effects; prostate cancer; radiotherapy