NES1基因联合188Re内放射治疗前列腺癌的实验研究

项目名称： NES1基因联合188Re内放射治疗前列腺癌的实验研究

项目编号： No.81501502

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡佳佳

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 目前对于雄激素非依赖前列腺癌(AIPC)尚缺乏有效治疗方法。本课题组前期研究表明正常上皮细胞特异性-1（NES1）基因在AIPC细胞株（PC3）中为抑癌基因，过表达NES1可下调癌基因Bcl-2表达，促进肿瘤细胞凋亡。据此，我们拟进一步阐明NES1在PC3中下调Bcl-2的机制及相关信号通路，从而揭示NES1对PC3的抑癌机制。最新研究显示下调Bcl-2对前列腺癌放疗具有增敏作用，本研究拟利用已制备的重组双基因NES1-IRES-hNIS慢病毒稳转获得的双基因表达PC3细胞及其荷瘤裸鼠模型，探究过表达NES1下调Bcl-2促凋亡联合人钠碘同向转运体（hNIS）介导188Re的内放射治疗对肿瘤促凋亡、内放疗增敏的多重抑癌作用，同时hNIS作为报告基因显像在体动态评估疗效，为今后AIPC联合治疗与疗效监测同步的多模态治疗方案提供理论依据。

中文关键词： 钠碘同向转运体；正常上皮细胞特异性-1；雄激素非依赖前列腺癌；信号通路；报告基因显像

英文摘要： For those patients suffered with the androgen-independent prostate cancer (AIPC) is still lack of effective treatment methods currently. Our previous study demonstrated: ①the role of normal epithelial cell specific -1 (NES1) gene as a tumor suppressor gene in AIPC cell line (PC3); ②the down-regulation of Bcl-2 expression and the apoptosis promotion in NES1 over-expressed PC3 cell line. On this basis, we intend to go a step further to demonstrate the mechanism of Bcl-2 controlled by NES1 in PC3 cell line, and to explore the relative signal pathway, in the purpose of revealing the molecular mechanism of NES1 in PC3 inhibition. In view of recent literatures, which reported the radiosensitizing effects of Bcl-2 down-regulated on radiotherapy for prostate cancer, this study aims to utilize the dual-gene expressed PC3 cell line, stably transfected by recombinant NES1-IRES-hNIS lentivirus, and the PC3 xenograft nude mice model, to explore the multiple anti-tumor effects of apoptosis promotion and 188Re internal radiosensitizing in the result of Bcl-2 down-regulated, via combining over-expressed NES1 gene therapy and 188Re internal radiotherapy mediated by human sodium iodidesymporter (hNIS); besides, to synchronously monitor NES1 gene expression and evaluate curative therapeutic effects in vivo through the hNIS reporter gene imaging. This study is in the purpose of establishing the theoretical basis for future AIPC multimodal therapy scheme that integrates the combined treatments and therapeutic monitoring synchronously.

英文关键词： hNIS;NES1;AIPC;signal pathway;reporter gene imaging