基因工程单纯疱疹病毒-1 KTR27治疗骨肉瘤的实验研究  

Effect of a novel oncolytic herpes simplex virus KTR27 on nude mouse model of human osteosarcoma

作　　者：王迪凡[1] 徐立辉[2] 吴杰[1] 

机构地区：[1]首都医科大学附属北京友谊医院骨科,北京100050 [2]北京大学第四临床医学院北京积水潭医院骨肿瘤科,北京100035

出　　处：《中华骨与关节外科杂志》2017年第4期341-346,共6页Chinese Journal of Bone and Joint Surgery

摘　　要：背景:近年来,骨肉瘤的治疗处于一个平台期,探索新的治疗方式成为广泛的共识。随着肿瘤分子生物学和基因工程学的发展,使用溶瘤病毒治疗恶性肿瘤成为一个热点。目的:探讨基因工程单纯疱疹病毒-1(herpes simplex virus 1,HSV-1)KTR27对骨肉瘤细胞系U2OS的体外作用以及裸鼠骨肉瘤模型局部原发肿瘤的作用。方法:采用体外实验观察KTR27对U2OS细胞系的细胞致病作用。裸鼠皮下注射人骨肉瘤细胞株U2OS,建立骨肉瘤裸鼠模型,在此基础上将动物模型随机分为6组,2组为空白对照,分别喂饲普通鼠粮和含强力霉素的鼠粮;2组瘤内注射KTR27(1×107PFU/50μl),喂饲普通鼠粮和含强力霉素的鼠粮;2组瘤内注射DMEM 50μl,喂饲普通鼠粮和含强力霉素的鼠粮。计算肿瘤体积并绘制肿瘤生长曲线,同时行组织学检查。结果:体外实验显示KTR27对U2OS有明显的致病作用,形成空斑。成功建立U2OS细胞系的骨肉瘤裸鼠模型并得到肿瘤生长曲线,注射KTR27后测量各组肿瘤体积大小,显示各组肿瘤体积无显著性差异(P>0.05)。各组肿瘤体积时间变化曲线分析显示,各组的时间趋势不同,相比较有统计学差异(P<0.05)。可见注射KTR27的肿瘤生长趋势受到抑制,与加用强力霉素后没有显著性差异(P>0.05)。注射KTR27后24 h病理切片显示肿瘤坏死增加,但7 d后肿瘤局部恢复增长。结论:基因工程HSV-1 KTR27对U2OS细胞有明显的细胞致病作用。使用U2OS细胞系建立裸鼠皮下骨肉瘤模型,然后局部瘤内注射基因工程HSV-1 KTR27,肿瘤的生长趋势受到了抑制,加用强力霉素后这种抑制没有明显区别。Background：In recent years the treatment of osteosarcoma has been on a plateau and it is necessary to explore new ways.With the development of tumor molecular biology and genetic engineering,oncolytic virus has become a hot spot due to its effect in treatment of malignant tumors.Objective：To investigate the effect of a novel oncolytic herpes simplex virus KTR27 on U2OS,a human osteosarcoma cell line,in vitro and nude mouse model of osteosarcoma with local primary tumor.Methods：Observe the cytopathogenic effect of KTR27 on U2OS cell through in vitro experiment.U2OS cell strain was injected into nude mice subcutaneously to establish nude mouse models of osteosarcoma,which were randomly divided into six groups including two blank control groups fed with common food and special food with tetracycline respectively;two groups injected with KTR27 of 1 × 10^7 PFU/50 μl intratumorally and fed with common food and special food with tetracycline respectively;two groups injected with DMEM 50 μl intratumorally and fed with common food and special food with tetracycline respectively.Measure and calculate the volume of tumors.Set up and compare the growth curve.Histological examination was carried out.Results：In vitro experiment showed that KTR27 had an obvious cytopathogenic effect on U2OS cell and many plaques were formed in cell culture.Nude mouse models of osteosarcoma by U2OS cell strain were successfully established and tumor growth curves were obtained.Tumor volumes of all groups were measured after KTR27 injection,and there were no significant difference among groups （P〉0.05）.The volume-time variation curves of all groups showed that the time tendency was significantly different among groups （P〈0.05）.After KTR27 injection,the tumor volume reduced and the tumor growth tendency was suppressed,and there was no significant difference between mice fed with common food and mice fed with special food with tetracycline （P〉0.05）.An increased tumor necrosis at 24 h after KTR27 injection was shown but

关 键 词：骨肉瘤 裸鼠 溶瘤病毒 单纯疱疹病毒 

分 类 号：R738[医药卫生—肿瘤]