Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models
文献类型：期刊论文
| 作者 | Fu, W; Chu, L; Han, XW; Liu, XY; Ren, DM |
| 刊名 | JOURNAL OF GENE MEDICINE
 |
| 出版日期 | 2008 |
| 卷号 | 10期号:6页码:690-701 |
| 关键词 | apoptosis-related cancer-specific therapy hTERT promoter orally attenuated S. typhimurium Smac/TRAIL synergistic effect |
| 通讯作者 | Ren, DM (reprint author), Fudan Univ, State Key Lab Genet Engn, Inst Genet, Shanghai 200433, Peoples R China.,dmren@fudan.edu.cn |
| 英文摘要 | Salmonella enterica Serovar Typhimurium (S. typhimurium), a facultative anaerobe, has been reported to be capable of both selectively amplifying and expressing exogenous genes within tumors. In addition, previous studies have demonstrated that the human telomerase reverse transcriptase (hTERT) promoter could confine gene expression strictly to the telomerase-positive cancer cells. In the present study, we used attenuated S. typhimurium as a carrier to deliver a eukaryotic expression vector (pSNhTS) that contains the second mitochondria-derived activator of caspases (Smac) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genes under the control of the hTERT promoter. The results of in vitro experiments showed that Smac could enhance TRAIL-induced apoptosis in tumor cells and the hTERT promoter could drive specific gene expression in tumor cells, but not in normal cells. In vivo data in mice indicated that salmonella-mediated exogenous gene expression could persist for at least 14 days in tumors. Furthermore, S.L./SNhTS (S. typhimurium carrying the pSNhTS) was orally administered into mice bearing tumors, and its antitumoral effect was evaluated. it was observed that S.L./SNhTS significantly inhibited tumor growth by 70-90% and prolonged the survival of mice. This strong antitumoral activity achieved by S.L./SNhTS was due to the synergistic antitumoral properties of Smac and TRAIL-recombinant proteins. Our data also support the idea that the hTERT promoter could be an excellent candidate for cancer-specific therapy and S. typhimurium appeared to be a promising strategy for the treatment of solid tumors. Copyright (C) 2008 John Wiley & Sons, Ltd. |
| 学科主题 | Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine |
| 类目[WOS] | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental |
| 关键词[WOS] | EXPRESSING BACTERIAL NITROREDUCTASE ; HUMAN CANCER-CELLS ; IN-VIVO ; ADENOVIRAL VECTOR ; BAX GENE ; THERAPY ; SMAC/DIABLO ; TRAIL ; ENDOSTATIN ; SENSITIZE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000257170400010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1394]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Fu, W,Chu, L,Han, XW,et al. Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models[J]. JOURNAL OF GENE MEDICINE,2008,10(6):690-701. |
| APA | Fu, W,Chu, L,Han, XW,Liu, XY,&Ren, DM.(2008).Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models.JOURNAL OF GENE MEDICINE,10(6),690-701. |
| MLA | Fu, W,et al."Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models".JOURNAL OF GENE MEDICINE 10.6(2008):690-701. |
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