摘要
目的:研究腺病毒介导的RNA干涉(RNA interfer-ence,RNAi)沉默存活素(Survivin)表达后,对MCF-7细胞裸鼠人乳腺癌移植瘤的抑制作用.方法:构建携带survivinshR-NA表达质粒的腺病毒Ad-survivin,并检测其滴度;建立人乳腺癌裸鼠移植瘤模型;将重组腺病毒悬液行瘤周和瘤体注射,观察肿瘤生长情况;剥离瘤体称重并计算药物的抑瘤率;免疫组织化学检测Survivin蛋白表达情况.结果:成功建立人乳腺癌肿瘤模型,移植瘤成功率为90%(18/20);给药后实验组移植瘤的生长速度慢于对照组;病理学检查为浸润性导管癌;剥离肿瘤组织称重发现实验组抑瘤率为28.89%(P<0.05);免疫组化发现实验组Survivin蛋白表达区的吸光度值为(15.63±1.54),明显低于阴性对照组(30.45±6.72)和空白对照组(30.25±6.58),差异均有统计学意义(P<0.05).结论:以腺病毒为载体,以survivin基因为靶点RNAi介导的基因治疗方法有望成为乳腺癌一种新的治疗策略.
AIM： To research the growth of human breast cancer in nude mice after Survivin is knocked down by RNAi. METHODS： We constructed recombinant adenovirus with shRNA expression vector of survivin, and detected its titre. MCF- 7 cells were injected into 20 nude mice to make the model of human breast cancer. The mice were treated with adenovirus, which carried the expression vector of survivin shRNA; the tumors were stripped and weighed to get the growth inhibition rate. Immunohistochemistry assay was done to detect the expression of Survivin. RESULTS： MCF-7 cells were seeded into nude mice and transplanted tumors were achieved in 90% （18/20） mice. Tumors of Ad-survivin group grew slower than the controls. All of the specimens were demonstrated as infiltrating ductal carcinoma. The growth inhibition rate of Ad-survivin group was 28. 89% （P 〈 0.05）. Optical density value of the survivin-expressed area was （15. 63± 1.54 ）, being lower than that of control groups （30.45 ±6.72, 30. 25 ±6.58, P 〈0.05）. CONCLUSION： With the help of adenovirus, gene therapy targetting survivin, which is mediated by RNAi, may be a strategy of curing human breast cancer.
出处
《第四军医大学学报》
北大核心
2008年第19期1792-1795,共4页
Journal of the Fourth Military Medical University
