Kouhpayeh S, Einizadeh A R, Hejazi Z, Boshtam M, Shariati L, Mirian M, Darzi L, Sojoudi M, Khanahmad H, Rezaei A
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Biology, International Pardis, University of Guilan, Rasht, Iran.
Cancer Gene Ther. 2016 Aug;23(8):254-7. doi: 10.1038/cgt.2016.26. Epub 2016 Jul 1.
Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone-refractory state and AR mechanism of action, this study was designed. A single-stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 °C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP).
前列腺癌通常会发展到对传统治疗方法无反应的激素难治性状态。因此，正在研发治疗侵袭性前列腺癌的新方法。鉴于雄激素受体（ARs）在激素难治性状态发展及AR作用机制中的重要性，开展了本研究。设计了一种可模拟激素反应元件（HRE）的单链DNA适配体。将富含AR的LNCaP细胞分为三组，每组三个重复：试验组用模拟HRE的适配体（AMH）转染，对照组仅接受转染试剂（mock）作为阴性对照。所有三组分别接受0、10和100 nM的脱氢表雄酮（DHEA）。数据分析显示，阴性对照组的LNCaP细胞在用10和100 nM DHEA处理后具有激素依赖性（与未处理的细胞相比，P=0.001）。与用10 nM（P=0.001）或100 nM DHEA处理的阴性对照组相比，AMH转染导致试验组细胞增殖显著减少（P=0.02）。AMH在37°C时可形成发夹结构并模拟基因组HRE。因此，它能够有效竞争基因组HRE并中断前列腺癌细胞系（LNCaP）中的雄激素信号通路。
