原位膀胱癌动物模型的建立及应用  

Establishment and Application of An Orthotopic Murine Bladder Cancer Model

作　　者：杨慎敏[1] 温端改[1] 侯建全[1] 何军 岑建农 陈剑华[3] 

机构地区：[1]苏州大学附属第一医院泌尿外科,江苏苏州215006 [2]江苏省血液研究所,江苏苏州215006 [3]苏州大学附属第一医院放射科,江苏苏州215006

出　　处：《癌症》2007年第4期341-345,共5页Chinese Journal of Cancer

基　　金：江苏省重点人才基金项目(No.RC2003094);江苏省卫生厅科技基金项目(No.H200517);江苏省社会发展基金项目(No.BS2005620);江苏省"六大人才高峰"项目(No.06-B-021)~~

摘　　要：背景与目的:表浅性膀胱癌术后膀胱灌注丝裂霉素等药物进行化疗,肿瘤仍有较高的复发率。有研究报道往膀胱内灌注小型干扰RNA(siRNA)可抑制裸鼠膀胱肿瘤生长。本研究目的是建立荷人膀胱癌的原位动物模型,通过磁共振成像(magnetic resonance imaging,MRI)监测肿瘤生长过程,并利用此模型评价靶向Survivin的干扰质粒对丝裂霉素的增效作用。方法:直视下经尿道机械损伤BALB/c裸鼠膀胱粘膜,将人膀胱癌细胞T24经尿道种植于25只裸鼠膀胱,建立荷人膀胱癌原位动物模型。以钆-二乙三胺五乙酸作为膀胱造影剂,用MRI监测肿瘤的生长,同时取裸鼠膀胱组织标本行HE染色进行病理学检查。同法建立膀胱癌裸鼠动物模型18只,分为对照组、丝裂霉素组和联合组3组,每周两次膀胱灌注,联合组为靶向Survivin的干扰质粒和丝裂霉素交替用药;膀胱灌注6次后荷瘤膀胱称重。结果:25只裸鼠在种植T24细胞后均形成膀胱肿瘤。种植后7天裸鼠膀胱MRI检查无明显变化,l4、21、28天MRI检查均可发现膀胱不同程度的充盈缺损,MRI图像与肿瘤实际大小吻合。病理检查显示:种植后7天,肿瘤生长于裸鼠膀胱粘膜或浅层肌肉;14～28天局限于肌层;35天时侵及浆膜层。丝裂霉素组和联合组的抑瘤率分别为33.45%、56.34%,联合组优于丝裂霉素组(P<0.05)。结论:成功建立了裸鼠原位膀胱癌动物模型,肿瘤生长基本模拟了人膀胱癌的发生、发展过程;MRI检查可作为对裸鼠膀胱原位肿瘤动态观察的可靠方法。靶向Survivin的干扰质粒增加了丝裂霉素的抗肿瘤作用。BACKGROUND ＆ OBJECTIVE： The recurrence rate of superficial bladder cancer is still high even the patients received postoperative intravesical infusion of chemotherapeutic drugs, such as mitomycin C （MMC）. Some studies showed that intravesical infusion of small interfering RNA（siRNA） could suppress the growth of bladder cancer in nude mice. This study was to establish an orthotopic animal model bearing human bladder cancer, monitor tumor progression by magnetic resonance imaging （MRI）, and observe the synergistic effect of survivin short hairpin RNA （shRNA） in combination with MMC for intravesical treatment using this animal model. METHODS： Human bladder cancer cell line T24 was inoculated into the bladders of 25 BALB/c nude mice to establish orthotopic bladder cancer model. MRI was performed to monitor tumor progression, using Gd-DTPA as contrast agent .The pathologic morphology of the bladders was observed. Eighteen mice bearing bladder cancer were randomized into 3 groups, untreated group, MMC group, and combination group. The bladders were weighed after 6 intravesical infusions. RESULTS： All the 25 mice developed bladder cancer after T24 cell inoculation. On MRI, no change in the bladders was observed at 7 days after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected at 14, 21, and 28 days after inoculation. Pathologic examination showed that tumors grew in mucosa of the bladders at 7 days after inoculation, infiltrated into muscle layer at 14-28 days after inoculation, and invaded serosa at 35 days after inoculation. The inhibition rate of tumor growth was significantly higher in combination group than in MMC group （56.34% vs. 33.45%, P〈0.05）. CONCLUSION： We successfully established an orthotopic bladder cancer model, which could simulate the progression of human bladder cancer approximately. MRI is a reliable way for dynamic detection of murine orthotopic bladder tumor. Down-regulating survivin expression by RNA interference could enhance

关 键 词：膀胱肿瘤 动物模型 磁共振成像 SURVIVIN 裸鼠 

分 类 号：R737.14[医药卫生—肿瘤] R-332[医药卫生—临床医学]