【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.更多还原

【Abstract】 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.更多还原