摘要
目的:探讨应用小分子干扰RNA(small interfering RNA,siRNA)沉默磷酸肌醇-3-激酶(phosphatidylinositol-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-U6-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-U6-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(P<0.01),平均生存时间显著延长(P<0.01);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。
Objective： To investigate the effect of silencing PI3K 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 （Psilencerl. 0-U6-PI3K） were constructed and xenografted tumor model was established in nude mice by subcutaneous inoculation of MCF-7 cells. Twenty-seven nude mice with xenografted tumor were divided randomly into 3 groups. Group 1 was intratumorally administered by Psilencerl. 0-U6-PI3K plasmid. Group 2 and group 3 were intratumorally given Psilencer10-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 measured by Western blotting. Results： The tumor size was significantly decreased and the average survival time was significantly enlongated in Psilencerl. 0-U6-PI3K-treated group （P 〈0.01 ）. Western blotting analysis showed that the protein expression of PI3K in xenografted tumor was markedly decreased and FOXO3a was significantly elevated compared with control groups （ P 〈 0.05 ）. Conclusion： Psilencerl. 0-U6-PI3K markedly silenced the expression of PI3K gene, up-regulated the expression of tumor suppressor gene FOXO3a, inhibited the growth of xenografted tumor, finally prolonged the survival time of nude mice bearing human breast carcinoma.
出处
《肿瘤》
CAS
CSCD
北大核心
2008年第4期310-312,共3页
Tumor
