• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International journal of oncology >Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella
【24h】

Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella

机译：通过沙门氏菌携带自杀性大肠杆菌嘌呤核苷磷酸化酶基因的基于Semliki Forest病毒的DNA载体的双重特异性抗肿瘤作用

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Escherichia coli purine nucleoside phospho-rylase/2-fluoro-2-deoxyadenosine (ePNP/F-dAdo) suicide system has demonstrated a powerful killing and bystander effects on tumor cells. However, several drawbacks to this approach remain to be resolved, such as the side-effects and the low efficiency of ePNP-targeted expression. A human telo-merase reverse transcriptase promoter-driven Semliki?Forest virus-based DNA vector (pShT-ePNP) with high expression of the ePNP gene was constructed. Live attenuated Salmonella typhimurium?7207 (SL7207) was used initially as a vehicle to targetly transfer the large alphavirus vector into tumor cells. The in?vitro quantitative analysis showed ~2-fold higher green fluorescent protein (GFP) expression for pShT-GFP than for conventional cytomegalovirus (CMV) promoter-mediated eukaryotic expression plasmids such as pIRES-GFP and the targeted expression of the ePNP gene in tumor cells was also detected by RT-PCR. After F-dAdo addition, the enzymatic conversion of F-Ado into 2-fluoroadmine (F-Ade) was tested by HPLC. Cell cytotoxicity assays showed that the significant inhibitory effect of the SL/pShT-ePNP system on tumor cells was dose- and time-dependent. Following oral administration, recombinant bacteria targetly allocated within the solid tumor and the expression of ePNP and GFP genes in?vivo were detected by RT-PCR or observed by fluorescence microscopy. SL/pShT-ePNP and F-dAdo were also found to exert powerful therapeutic effects in combination against tumor growth and for prolonging the lifespan of tumor-bearing mice. These findings suggest that the SL/pShT-ePNP system may serve as a powerful strategy for tumor therapy.
机译：大肠杆菌嘌呤核苷磷酸-rylase / 2-氟-2-脱氧腺苷（ePNP / F-dAdo）自杀系统已证明对肿瘤细胞具有强大的杀伤和旁观者作用。但是，此方法的一些缺点仍有待解决，例如副作用和ePNP靶向表达的低效率。构建了人类端粒酶逆转录酶启动子驱动的高表达ePNP基因的Semliki-Forest病毒DNA载体（pShT-ePNP）。减毒的鼠伤寒沙门氏菌？7207（SL7207）最初被用作将大的α病毒载体靶向转移到肿瘤细胞中的载体。体外定量分析显示，pShT-GFP的绿色荧光蛋白（GFP）表达比常规巨细胞病毒（CMV）启动子介导的真核表达质粒（如pIRES-GFP）高约2倍，而ePNP基因的靶向表达还通过RT-PCR检测到肿瘤细胞。在添加F-dAdo之后，通过HPLC测试F-Ado向2-氟施用（F-Ade）的酶促转化。细胞毒性试验表明，SL / pShT-ePNP系统对肿瘤细胞的显着抑制作用是剂量和时间依赖性的。口服后，通过RT-PCR检测或体内荧光显微镜观察到重组细菌在实体瘤内的靶向分布以及体内ePNP和GFP基因的表达。还发现SL / pShT-ePNP和F-dAdo具有强大的治疗作用，可共同对抗肿瘤生长和延长荷瘤小鼠的寿命。这些发现表明SL / pShT-ePNP系统可以作为一种强有力的肿瘤治疗策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号