血管内皮生长因子siRNA对人膀胱癌裸鼠移植瘤生长的实验研究  

Inhibiting effect of small interfering RNA targeting vascular endothelial growth factor on bladder carcinoma T24 xenograft

作　　者：刘禄成[1] 李然伟[1] 许宗革[2] 李哲[2] 高瑞娟[2] 

机构地区：[1]吉林大学第二医院泌尿外科,吉林长春130041 [2]吉林大学基础医学院细胞生物教研室,吉林长春130021

出　　处：《中国现代医学杂志》2008年第13期1814-1817,共4页China Journal of Modern Medicine

基　　金：国家自然科学基金资助项目(No:30571857);吉林省科学技术厅资助项目(No:200505118)

摘　　要：目的观察VEGF siRNA对人膀胱癌裸鼠皮下移植瘤生长的抑制作用,探讨VEGF作为膀胱癌基因治疗靶点的有效性。方法已稳定转染pGC-siVEGF的T24接种至裸鼠皮下,建立荷瘤裸鼠膀胱癌模型。利用免疫组织化学方法(SABC)检测肿瘤细胞VEGF和肿瘤间质CD34的水平,根据CD34表达情况评价肿瘤微血管密度(MVD),末端脱氧核苷酸转移酶标记法(TUNEL)测定肿瘤细胞凋亡指数。结果实验组与对照组相比较:成瘤率低,肿瘤生长速度缓慢(P<0.01);VEGF水平下降(P<0.01);肿瘤微血管密度减少(P<0.01);凋亡指数升高(P<0.01)。组间比较差异均具有显著性。结论以VEGF为靶点的小干扰RNA有抑制VEGF表达、遏制膀胱癌T24细胞在体内生长的作用,VEGF有可能成为临床膀胱癌基因治疗的有效靶点,为膀胱癌的抗血管生成疗法提供理论基础。[Objective] To observe the inhibitory effect of small interfering RNA targeting vascular endothelial growt.la factor （VEGF） on the growt.h of nude mice bladder carcinoma T24 xenograft. [Methods] The pGC-siVEGF stable-transfected T24 cells were subcutaneously injected into nude mice, to establish bladder carcinoma xenograft nude mice model. Tumor growth in nude mice was monitored, and the tumor tissues were immunostainned to analyze the expression level of VEGF and CD34, by which the microvessel density （MVD） was determined. Cell apoptosis in xenograft tumors was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling （TUNEL）. [Results] After subcutaneous inoculation with pGC-siVEGF transfected T24 cells, tumor growth in nude mice was significantly inhibited （P 〈0.01） and VEGF expression and MVD were statistically decreased （P 〈 0.01）. There were much more apoptotic cells in treated groups compared to that in controls （P 〈0.01）. [Conclusion] VEGF siRNA could knock down VEGF expression and inhibit tumor growth in xenograft model of bladder carcinoma. VEGF could be an effective target for gene therapy of clinical bladder carcinoma, and it supplied strong thereotieal basis for antiangiogenie therapy of bladder cancer.

关 键 词：膀胱癌 血管内皮生长因子 小干扰RNA 细胞凋亡 裸鼠 

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