雄激素受体三螺旋形成寡核苷酸抗前列腺癌细胞增殖的研究  

Antiproliferation effects of a androgen receptor triple-helix forming oligonucleotide on prostate cancer cells

作　　者：张勇[1] 陈维真[1] 谢瑶[2] 高锦辉[3] 

机构地区：[1]中山大学附属第三医院核医学科,广州510630 [2]中山大学基础医学院解剖学教研室 [3]中山大学基础医学院实验核医学教研室

出　　处：《中华核医学杂志》2005年第2期97-99,共3页Chinese Journal of Nuclear Medicine

基　　金：广东省自然科学基金项目 (0 1 0 738);广东省医学科学基金项目 (B2 0 0 0 0 4 8)

摘　　要：目的　探讨反基因策略对雄激素受体(AR)表达和前列腺癌细胞增殖的影响。方法　针对AR基因2 4 4 7～2 4 6 1核苷酸序列设计并合成三螺旋形成寡核苷酸(TFO) ,经脂质体介导转染LN CaP前列腺癌细胞株,于转染后2 4、4 8、72h分别采用3H 胸腺嘧啶核苷(TdR)参入实验测定癌细胞增殖活性,用逆转录聚合酶链反应(RT PCR)方法检测ARmRNA表达,用放射配基结合分析法(RBA)单点法检测AR蛋白质表达,并与反义寡核苷酸(ASON)相比较。结果　2 4、4 8、72hTFO组LNCaP细胞的AR表达水平明显低于ASON组(P <0 0 5 ) ,TFO对LNCaP细胞增殖的抑制率显著高于ASON(P <0 0 5 )。结论　该TFO能有效抑制AR表达和前列腺癌细胞增殖。Objective To provide experimental basis for antigene radiation therapy through exploring the effects of antigene strategy on androgen receptor (AR) expression and proliferation of prostate cancer cells. Methods The triple helix forming oligonucleotide (TFO) targeting 2447～2461nt of AR cDNA was designed and transfected LNCaP prostate cancer cells with liposome. 24～72 h after transfection, the cellular proliferation was detected by 3H thymidine (TdR) incorporation test, the expression of AR gene was examined by reverse transcription polymerase chain reaction (RT PCR) and expression of AR protein was performed by radioligand binding assay. The results of TFO were compared with antisense oligonucleotide (ASON). Results At all time points, the AR expression levels in TFO group were markedly lower than that of ASON group( P <0.05). The inhibitory rate of TFO for cellular proliferation was significantly higher than that of ASON ( P <0.05). Conclusion The TFO was a potent inhibitor for AR expression and cell proliferation of LNCaP cells, and could be used in antigene radiotherapy.

关 键 词：前列腺癌细胞增殖 三螺旋形成寡核苷酸 雄激素受体 逆转录-聚合酶链反应(RT-PCR) 放射配基结合分析法 前列腺癌细胞株 LNCAP细胞 细胞增殖活性 胸腺嘧啶核苷 mRNA表达 反义寡核苷酸 反基因策略 脂质体介导 蛋白质表达 序列设计 

分 类 号：R737.25[医药卫生—肿瘤] R373.21[医药卫生—临床医学]