siRNA沉默PI3K基因激活FoxO3a基因并抑制人乳腺癌裸鼠移植瘤生长的实验研究.pdfVIP

· 310· 肿瘤2008年4月第28卷第4期 TumorVo1．28，No．4，April，2008 DOI：10．3781／j．issn．1000—7431．2008．04．OO9 警 ： 咖 -=-：毒謦书戋．| siRNA沉默PI3K基因激活FoxO3a基因并抑制人乳腺癌裸鼠移植瘤生 长的实验研究 黄伟翼，靖大道，沈 赞 (上海交通大学附属第一人民医院肿瘤科，上海 200080) [摘要] 目的：探讨应用小分子干扰RNA(small interfering RNA，siRNA)沉默磷酸肌醇一3．激酶(phosphatidylinositol一3 kinase， PI3K)基因对人乳腺癌细胞MCF-7中抑癌基因FoxO3a的表达及人乳腺癌裸鼠移植瘤模型的肿瘤生长的影响。方法：构建 PI3K基因siRNA质粒Psilencer1．0一U6一PI3K—siRNA；乳腺癌细胞株MCF-7裸鼠背部皮下接种，建立人乳腺癌裸鼠移植瘤动物 模型，成瘤后将实验动物分3组，每组9只，1组注射Psilencer1．0一U6一PI3K—siRNA质粒、另2组分别注射Psilencer1．0．U6空质 粒或0．9％的氯化钠溶液作为对照。观察肿瘤体积变化、裸鼠生存时间；并用Western印迹法检测瘤组织中FoxO3a和PI3K的 表达。结果：PI3K—siRNA质粒治疗组裸鼠的肿瘤体积明显缩小(P0．01)，平均生存时间显著延长(P0．01)；肿瘤内PI3K 基因表达水平明显下降，而FoxO3a基因的表达水平明显升高。结论：PI3K基因siRNA能够明显抑制人乳腺癌裸鼠移植模型 的PI3K基因的表达，上调抑癌基因FoxO3a的表达，抑制肿瘤生长，延长荷瘤鼠的生存时间。 [关键词] 乳腺肿瘤；异种移植模型抗肿瘤试验；RNA干扰；磷脂酸肌醇3一激酶；小鼠，裸 [中图分类号] R737．9；R73—36 2 [文献标志码] A [文章编号] 1000—7431(2008)04-0310-03 Silencing PI3K by siRNA activated FoxO3a gene and inhibited the growth of xenografted breast carcinoma in nnde mice HUANG Wei—yi，JING Da—dao，SHEN Zan (Department of Oncology，Shanghai First People’s Hospital。Shanghai Jiaotong Uni— versity，Shanghai 200080，China) [ABSTRACT] Objective：To investigate the effect of silencing PI3 K by small interfering RNA(siRNA)on the expression of FOXO3a in human breast cancer MCF-7 cells and the growth of xenografted breast carcinoma in nude mice．Methods：Plasmids of siRNA for PI3K gene(Psilencer1．0-U6一PI3K)were constructed and xenografted tumor model was established in nude mice by subcuta— neous inoculation of MCF-7 cells．Twenty—seven nude mice with xenografted tumor were divided randomly into 3 groups．Group 1 was intratumorally administered by Psilencer1．0-U6一PI3K plasmid．Group 2 and group 3 were intratumorally舀ven Psilencerl0一U6 plasmid and physiological saline(group 1)，respectively．The tumor volume and survival time of nude mice were recorded．The expressions of PI3K and FOXO3a was measu