Wang Wei, Chen Mei-Nan, Cheng Kai, Zhan Li-Li, Zhang Jie
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Exp Ther Med. 2014 Aug;8(2):635-641. doi: 10.3892/etm.2014.1751. Epub 2014 Jun 2.
This study aimed to investigate the lethal effect of the combination of bluetongue virus (BTV) and radiation on RM-1 murine prostate cancer cells and . 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 assessed and the combined effect was also assessed in tumor models . 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 effect and . 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 cells and compared 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.
本研究旨在探究蓝舌病毒(BTV)与辐射联合作用对RM-1小鼠前列腺癌细胞的致死效应。用BTV感染各种细胞系,并通过乳酸脱氢酶(LDH)释放生物测定法检测细胞毒性。此外,用辐射和/或BTV处理RM-1细胞,采用细胞计数试剂盒-8法评估细胞活力。通过荧光激活细胞分选(FACS)检测RM-1细胞的凋亡水平。为确定辐射诱导BTV溶瘤活性变化的可能机制,进行了细胞周期分析。评估了BTV和放疗不同方案对细胞毒性的影响,并在肿瘤模型中评估了联合效应。结果表明,BTV对RM-1和PC-3癌细胞具有选择性细胞毒性,但不影响正常细胞,特别是人脐静脉内皮细胞和平滑肌细胞。与单独使用每种药物相比,BTV与辐射联合增强了细胞毒性,并具有协同效应。FACS结果证实,放疗诱导凋亡,BTV单独作用也诱导凋亡,联合治疗产生的凋亡水平最显著,且在早期最高。细胞周期分析表明,照射后再感染BTV,G2-M期水平升高。总之,与单独的任何一种治疗相比,BTV与放疗联合对RM-1细胞具有增强的细胞毒性,并显示出协同疗效,此外还有显著的诱导凋亡作用。这些结果支持未来对BTV在前列腺癌患者中潜在临床应用的研究。