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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

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【作者】 杨栓平宋三泰宋海峰郑晓玲汤仲明

【Author】 YANG Shuan Ping 1, SONG San Tai 1, SONG Hai Feng 2* , ZHENG Xiao Ling 1, TANG Zhong Ming 2 (1. Affiliated Hospital, 2. Department of Pharmacology, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China)

【机构】 军事医学科学院附属医院军事医学科学院放射医学研究所军事医学科学院放射医学研究所 北京100850北京100850北京100850

【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HER 2表达有关

【Abstract】 AIM 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.

【基金】 国家自然科学科学基金资助项目 (30 0 70 895 )~~
  • 【文献出处】 中国药理学与毒理学杂志 ,Chinese Journal of Pharmacology and Toxicology , 编辑部邮箱 ,2003年02期
  • 【分类号】R73-36
  • 【被引频次】1
  • 【下载频次】50
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