靶向survivin的siRNA对裸鼠肾癌移植瘤生长的影响  

Inhibitory effect of survivin-targeting siRNA on transplanted tumor growth of renal carcinoma in nude mice

作　　者：刘富[1] 胡自力[1] 

机构地区：[1]重庆医科大学附属第二医院泌尿外科,重庆400010

出　　处：《第三军医大学学报》2011年第6期582-585,共4页Journal of Third Military Medical University

基　　金：重庆市卫生局项目(2008-2-228)~~

摘　　要：目的观察生存素(survivin)小干扰RNA(siRNA)在体内是否能抑制肾癌移植瘤体的生长。方法 BALB/c雌性裸鼠皮下种植786-O细胞,将成瘤阳性的裸鼠按照随机区组法分为8组(A^H组),每组5只。选取2组survivin序列特异性双链RNA(double-stranded RNA,dsRNA),导入裸鼠皮下肾癌移植瘤。观察各组裸鼠体内瘤体生长速度,绘制肿瘤生长曲线,采用PCR、Western blot技术测定肿瘤组织的survivin基因表达水平,原位末端标记技术(TUNEL)检测细胞凋亡。结果 A组(survivin1 siRNA+脂质体+纯RPMI1640)、B组(survivin2 siRNA+脂质体+纯RPMI1640)较其他对照组(C^H组)裸鼠皮下移植瘤生长缓慢;取出瘤体,肿瘤体积明显缩小(P<0.05),survivin基因表达下调(P<0.05),肿瘤组织标本可见大量细胞核呈黄褐色、核质浓缩、细胞形态不规则的凋亡细胞(P<0.01)。结论 RNA干扰明显抑制靶基因survivin在肾癌786-O细胞裸鼠皮下移植瘤中的表达及肿瘤细胞增殖,并诱导细胞凋亡,且特异性好。Objective To study the effect of small interfering RNA（siRNA） targeting survivin gene on the growth of transplanted tumors of renal carcinoma in nude mice in vivo.Methods Human renal carcinoma 786-O cells were used to subcutaneously inoculate into BALB/c female nude mice to develop a transplanted tumor model of human renal carcinoma.When the tumor diameter reached 5 to 6 mm,forty tumor-carrying nude mice were randomly divided into eight groups（five for each group）.Two groups of the mice were treated by survivin-specific double-stranded RNA（dsRNA） via intratumoral injection,i.e.,group A（pGenesil1.1-survivin1） and group B（pGenesil1.1-survivin2）.Tumor volumes in each group were calculated every day.On the 18th day after the first intratumoral injection,all the mice were sacrificed and the tumors were taken out to undergo RT-PCR and Western blotting to detect survivin expression.Tumor cell apoptosis was detected by TUNEL assay.Results The mice in groups A and B indicated slower tumor growth,significantly smaller tumor volume（P0.05）,and lower survivin expression level（P0.05） in comparison with those in the control groups.The TUNEL results showed a large amount of apoptotic cells with tawny nuclei,condensed chromatin and irregular cell shapes in groups A and B（P0.01）.Conclusion RNA interference can obviously and specifically down-regulate survivin gene expression,inhibit cell proliferation and induce cell apoptosis in the transplanted tumors of human renal carcinoma in nude mice.

关 键 词：RNA干扰 肾肿瘤 SURVIVIN 细胞凋亡 

分 类 号：R73-362[医药卫生—肿瘤] R730.23[医药卫生—临床医学]