水泡口炎病毒在人前列腺癌模型的溶瘤效应
Oncolytic efficacy of recombinant vesicular stomatitis viruses in human prostate carcinoma model
目的 探讨利用水泡口炎病毒(VSV)作为一种新型药物治疗前列腺癌的可能性.方法 (1)确定VSV-绿色荧光蛋白(GFP)在不同时段对癌细胞的细胞毒性作用;(2)利用DU145细胞在裸鼠建立动物肿瘤模型,荷瘤动物经注射不同剂量的VSV-GFP(1×106、1×107 PFU/100μ1)后,观察不同时间点肿瘤的变化及治疗效果,并确定瘤体内病毒的复制水平、肿瘤大小变化及动物生存期的相关性.结果 VSV-GFP能选择性地杀伤前列腺癌细胞,在转染倍数(MOI) =0.1时,DU145细胞死亡率>85%,与之比较,RWPE-1细胞死亡率<20%,而RPMI 1640对照组细胞死亡率<5%.体内实验中,移植瘤体内不同时间点(12、24、48 h)病毒复制滴度分别为2.36×107 PFU/g、3.82×107 PFU/g、4.38×107 PFU/g,1×107 PFU剂量组,1×106 PFU剂量组,RPMI 1640对照组在治疗48 d后,移植瘤平均体积分别为(1470.54±480.67)、(903.40±3245.50)、(408.54±224.40)mm3,3组比较差异有统计学意义(P<0.05),与注射不含病毒RPMI 1640对照组比较,肿瘤明显缩小,动物生存期延长.结论 溶瘤病毒VSV-GFP在DU145为模型的体内、外实验中具有较好的治疗效果.
更多Objective To investigate the use of vesicular stomatitis virus (VSV) as a new way in the treatment of prostate cancer.Methods Study of recombinant virus VSV oncolytic effect in human prostate cancer in vivo,in vitro models and characteristics,(1) Includes:determining the cytotoxic effect of VSV in different periods of cancer cells; (2) the DU145 cells to establish animal model of tumor in nude mic e,VSV virus tumor-bearing animal by injection of different doses (1 × 106,1 × 107 PFU/100 μl),the change and the effect of treatment of different time points of the tumor,and to determine the correlation between replication level and tumor intratumoral virus size change and animal survival.Results VSV-green fluorescent protein (GFP) can selectively kill prostate cancer cells,MOI =0.1 DU145 cells,> 85% mortality,compared with RWPE-1 cell death,< 20%,and RPMI 1640 control group cell mortality rate < 5%.In vivo experiments,transplantation tumor in different time points (12,24,48 h) virus titer were (2.36 × 107 PFU/g,3.82 × 107 PFU/g,4.38 × 107 PFU/g),1 × 107 PFU dose group,1 × 106 PFU dose group,the RPMI 1640 control group after 48 d of treatment,the average volume of the transplanted tumors were approximately (1470.54 ± 480.67),(903.40 ± 3245.50),(408.54 ± 224.40) mm3,compared three groups,the difference was statistically significant (P < 0.05),and the injection contains no virus RPMI 1640 compared to the control group,the tumor was significantly reduced,prolong the survival of the animal.Conclusion Oncolytic virus VSV in DU145 model in vivo,in vitro experiments with a better therapeutic effect,showing that a certain application prospects.
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