CAJ | 학술논문

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.
목적 탐토이용수포구염병독(VSV)작위일충신형약물치료전렬선암적가능성.방법 (1)학정VSV-록색형광단백(GFP)재불동시단대암세포적세포독성작용；(2)이용DU145세포재라서건립동물종류모형,하류동물경주사불동제량적VSV-GFP(1×106、1×107 PFU/100μ1)후,관찰불동시간점종류적변화급치료효과,병학정류체내병독적복제수평、종류대소변화급동물생존기적상관성.결과 VSV-GFP능선택성지살상전렬선암세포,재전염배수(MOI) =0.1시,DU145세포사망솔＞85％,여지비교,RWPE-1세포사망솔＜20％,이RPMI 1640대조조세포사망솔＜5％.체내실험중,이식류체내불동시간점(12、24、48 h)병독복제적도분별위2.36×107 PFU/g、3.82×107 PFU/g、4.38×107 PFU/g,1×107 PFU제량조,1×106 PFU제량조,RPMI 1640대조조재치료48 d후,이식류평균체적분별위(1470.54±480.67)、(903.40±3245.50)、(408.54±224.40)mm3,3조비교차이유통계학의의(P＜0.05),여주사불함병독RPMI 1640대조조비교,종류명현축소,동물생존기연장.결론 용류병독VSV-GFP재DU145위모형적체내、외실험중구유교호적치료효과.
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.