应用“decoy”技术靶向性阻断Stat3对乳腺癌细胞系MDA-MB-231增殖抑制的研究  

Study of blockading Stat3 by transcription factor decoy-ODN inhibiting the proliferation of breast cancer cell line MDA-MB-231

作　　者：包建玲[1] 王淑芬[1] 张须龙[2] 张建[2] 

机构地区：[1]山东省医学科学院基础医学研究所,济南250062 [2]山东大学药学院免疫药理与免疫治疗学研究所,济南250012

出　　处：《中国免疫学杂志》2006年第11期1006-1009,共4页Chinese Journal of Immunology

基　　金：国家重点基础研究发展规划973资助项目(2004CB518807);国家自然科学基金项目(30571696)

摘　　要：目的应用针对核转录信号子和激活子3(Stat3)的诱骗寡核苷酸序列(decoy-ODN)阻断乳腺癌细胞系的增殖及其机制研究。方法阳离子聚合物介导ODN转染乳腺癌细胞系MDA-MB-231,通过细胞计数检测转染Stat3decoy-ODN及随机序列核苷酸(scrambleODN)后的细胞系增殖能力;流式细胞术(FCM)检测转染后细胞周期变化;荧光显微镜观察荧光标记的decoy-ODN转染效率;RT-PCR及Westernblot法分别检测Stat3下游抗凋亡基因在转录水平和蛋白水平的变化。结果转染Stat3Decoy-ODN序列后MDA-MB-231细胞的增殖受到了明显抑制(P<0.05);Stat3下游基因Bcl-xl、c-myc和CylinD1在转录水平和蛋白表达水平均明显降低。结论Stat3decoy-ODN通过抑制乳腺癌细胞系JAKs/STAT3通路从而抑制了细胞增殖,提示可以通过诱骗技术阻断肿瘤生长而达到基因治疗目的。Objective ：To investigate the mechanisms of decoy ohgodeoxynucleotides （decoy-ODN） blockading Stat3 that inhibit breast cancer cells MDA-MB-231 proliferation. Methods： Stat3 decoy-ODN and scramble control were transfected into breast cell line MDA-MB-231, respectively. The cell proliferation capability was detected by cell counting; flow cytometry was applied to detect MDAMB-231 cell cycle; FITC labeled decoy was observed by Reflected Light Fluorescence Microscope; the expression of the gene controlled by Star3 was examined by means of RT-PCR and Western blot assay. Results：Stat3 decoy-ODN could be internalized into MDA-MB- 231 cells and inhibit the growth of MDA-MB-231 cell via inducing its apoptosis. Stat3 decoy-ODN also could significantly reduce the expression of Stat3 controlling genes such as Bcl-xl, c-myc and CylinDl. Conclusion： Stat3 decoy-ODN can inhibit breast cell line MDA-MB-231 proliferation by blockading JAK/STAT pathway. This suggests that transcription factor decoy-ODN may serve as a novel therapeutic strategy for breast cancer.

关 键 词：乳腺肿瘤 DECOY STAR 寡核苷酸 

分 类 号：R73[医药卫生—肿瘤]