一个新的靶向HER-2 mRNA的反义寡核苷酸,HA824,对HER-2表达的影响(英文)  

Effect of a new antisense oligodeoxyribonucleotide,HA824,targeting at HER-2 mRNA on HER-2 expression

作　　者：杨栓平[1] 宋三泰[1] 宋海峰[2] 郑晓玲[1] 汤仲明[2] 

机构地区：[1]军事医学科学院附属医院,北京100850 [2]军事医学科学院放射医学研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2003年第2期87-92,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学科学基金资助项目 (30 0 70 895 )~~

摘　　要：目的　观察HA82 4 ,这种新合成的靶向HER 2mRNA的反义寡核苷酸对SK BR 3乳癌细胞株mRNA和蛋白表达的特异性作用。方法　以HA4为阳性对照 ,随机序列为随机对照检测了HA82 4对SK BR 3细胞生长的抑制作用与IC50 值 ;采用逆转录聚合酶链反应 (RT PCR)、流式细胞技术、免疫组织化学法检测了对SK BR 3细胞mRNA与蛋白表达的影响。结果　结果表明HA82 4对SK BR 3乳癌细胞的生长有剂量依赖性的抑制作用〔IC50 (nmol·L- 1) :HA82 4 ,(47± 2 6 ) ;HA4 ,(97± 4 1) ;随机序列 ,(2 5 1± 86 )。HA82 4vsHA4 ,P <0 .0 5〕。HA82 4还显著抑制了HER 2mRNA与蛋白的表达 (免疫组化结果 :HA82 4 ,1+染色 ;HA4 ,2 +染色 ;随机序列 ,3+染色 ;流式细胞技术检测结果 ,荧光强度分别为 :HA82 4 ,338.6 ;HA4 ,35 5 .5 ;随机序列 ,5 32 .4 )。结论HA82 4对SK BR 3乳癌细胞生长的抑制作用与特异性的抑制HERAIM To observe specific effect of HA824, a new synthesized antisense oligodeoxyribonucleotide(ODN), HA824, targeting at HER 2 mRNA on HER 2 expression in SK BR 3 breast cancer cells in mRNA and protein levels. METHODS Antisense ODN HA824 targeting at HER 2 mRNA was synthesized as our previous description. Growth inhibition effect, mean(n=3-5) 50% inhibitory concentrations (IC 50 ) on proliferations of SK BR 3 cells for HA824, HA4 and scramble were evaluated. HA824 on HER 2 mRNA and protein expression were examined by means of RT PCR, flow cytometry and immunohistochemistry. RESULTS The results indicated HA824 inhibited proliferation of SK BR 3 cells in a dose dependent manner 〔IC 50 (nmol·L -1 ): HA824, (47±26); HA4, (97±41); scramble, (251±86). HA824 vs HA4, P<0.05〕. HA824 also significantly suppressed HER 2 mRNA and protein expression detected by RT PCR , immunohistochemistry(HA824, light staining; HA4, moderate staining; scramble, heavy staining) and flow cytometry(fluorescence intensity: HA824, 338.6; HA4, 355.5; scramble, 532.4). CONCLUSION Not only can this kind of new synthesized antisense compound suppressed proliferation of SK BR 3 breast cancer cells, but also specially inhibited HER 2 expression in mRNA and protein levels.

关 键 词：乳腺癌 SK-BR-3细胞 HA824 HER-2 反义寡核苷酸 蛋白表达 逆转录聚合酶链反应 

分 类 号：R73-36[医药卫生—肿瘤]