敲减基质金属蛋白酶-10抑制人膀胱癌T24细胞系裸鼠皮下移植瘤生长  

The role of MMP-10 in the growth of human bladder cancer xenograft

作　　者：屈卫星[1] 惠荣[1] 陈伟[2] 丁上书[2] 程永毅[1] 贺大林[2] 

机构地区：[1]西安交通大学医学院第三附属医院泌尿外科,陕西西安710068 [2]西安交通大学医学院第一附属医院泌尿外科,陕西西安710061

出　　处：《现代肿瘤医学》2011年第10期1937-1940,共4页Journal of Modern Oncology

基　　金：陕西省自然科学基础研究计划项目(编号:SJ08-ZT09)

摘　　要：目的:探讨敲减MMP-10对人膀胱癌T24细胞系裸鼠皮下移植瘤生长的影响。方法:设计并合成针对人MMP-10的siRNA及阴性对照siRNA,分别注射至裸鼠皮下膀胱癌T24细胞系移植瘤,每周两次监测并比较各组裸鼠体重、瘤体大小,于接种后第5周处死裸鼠,取出皮下移植瘤,并比较各组瘤体重量的差异,并通过免疫组织化学染色检测MMP-10表达水平。结果:皮下注射膀胱癌T24细胞建立裸鼠皮下移植瘤模型,成瘤率达100%。瘤体内注射MMP-10 siRNA可以显著抑制膀胱癌T24细胞裸鼠皮下移植瘤的生长(P<0.05);观察结束时MMP-10 siRNA组所剥离的瘤体重量明显低于对照组(P<0.05)。各组裸鼠的平均体重并没有明显改变(P>0.05),提示瘤体内注射MMP-10 siRNA对裸鼠的一般情况影响不大,并没有明显的毒性或副作用。免疫组织化学染色结果示MMP-10 siRNA组MMP-10的染色强度及阳性细胞数均明显低于普通成瘤组和阴性对照组,提示瘤体内注射siRNA可以在体内有效敲低MMP-10的表达。结论:MMP-10在人膀胱癌T24细胞裸鼠皮下移植瘤的生长过程中发挥重要作用;瘤体内注射MMP-10 siRNA可以有效且安全地抑制膀胱癌T24细胞裸鼠皮下移植瘤的生长。Objective：To investigate the role of MMP-10 in the growth of bladder cancer.Methods： The model of bladder cancer xenograft was established by injection of human bladder cancer cell T24 subcutaneously.The effects of intra-tumoral injection of MMP-10 siRNA on the growth of xenograft were evaluated.The tumor volume and body weight was recorded twice weekly.At the end of experiment,tumors were excised,weighed,and then fixed in 4% paraformaldehyde for further analyses.The expression of MMP-10 in xenograft was assessed immuohistochemically.Results： After 7 days,100% of mice grew visible tumors.Intra-tumoral injection of MMP-10 siRNA significantly inhibited the growth of xenograft compared with control group（P0.05）,as further confirmed by the comparison of tumor weight（P0.05）.There were no changes on the body weight of nude mice in each group（P 0.05）.Immunostaining showed the downregulation of MMP-10 after intra-tumoral injection of MMP-10 siRNA compared with control group（P0.05）,suggesting the effective inhibition of MMP-10 in xenograft.Conclusion： Intra-tumoral injection of MMP-10 siRNA effectively inhibited the growth of human bladder cancer T24 in vivo,suggesting that MMP-10 plays a vital role in the growth of bladder cancer,which also provided a rationale for the development of gene therapy for the treatment of bladder cancer.

关 键 词：基质金属蛋白酶-10 膀胱癌 祼鼠 

分 类 号：R730[医药卫生—肿瘤] R737.14[医药卫生—临床医学]