Suppression of colorectal tumor growth by regulated survivin targeting
文献类型：期刊论文
| 作者 | Li, BH; Fan, JK; Liu, XR; Qi, R; Bo, LN; Gu, JF; Cheng, Q; Liu, XY |
| 刊名 | JOURNAL OF MOLECULAR MEDICINE-JMM
 |
| 出版日期 | 2006 |
| 卷号 | 84期号:12页码:1077-1086 |
| 关键词 | RU486-regulated system survivin dominant negative mutant hTERT promoter cancer-targeting therapy |
| 通讯作者 | Liu, XY (reprint author), Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Hangzhou 310018, Peoples R China.,xyliu@sibs.ac.cn |
| 英文摘要 | A major goal in cancer gene therapy is to develop efficient gene transfer protocols that allow tissue-specific and tightly regulated expression of therapeutic genes. The ideal vector should efficiently transduce cancer cells with minimal toxicity on normal tissues and persistently express foreign genes. One of the most promising regulatory systems is the mifepristone/RU486-regulated system, which has much lower basal transcriptional activity and high inducibility. In this work, we modified this system by incorporating a cancer-specific promoter, the human telomerase reverse transcriptase (hTERT) promoter. By utilizing hTERT promoter to control the regulator, RU486 could specifically induce the expression of foreign genes in cancer cells but not in normal cells. In the context of this system, a dominant negative mutant of survivin (surDN) was controllably expressed in colorectal tumor cells. The surDN expression induced by RU486 showed a dosage-and time-dependent pattern. Regulated expression of surDN caused caspase-dependent apoptosis in colorectal tumor cells but had little effect on normal cells. Analysis of cell viability showed that RU486-induced expression of surDN suppressed colorectal tumor cell growth and had synergic effect in combination with chemotherapeutic agents. The potential of this system in cancer therapy was evaluated in experimental animals. Tumor xenograft models were established in nude mice with colorectal tumor cells, and RU486 was intraperitoneally administered. The results showed that conditional expression of surDN efficiently inhibited tumor growth in vivo and prolonged the life of tumor-burdened mice. Synergized with the chemotherapeutic drug cisplatin, regulated surDN expression completely suppressed tumor growth. These results indicated that this modified RU486-regulated system could be useful in cancer-targeting therapy. |
| 学科主题 | Genetics & Heredity; Research & Experimental Medicine |
| 类目[WOS] | Genetics & Heredity ; Medicine, Research & Experimental |
| 关键词[WOS] | CATALYTIC SUBUNIT HTERT ; ANTI-APOPTOSIS GENE ; CANCER-CELLS ; THERAPEUTIC TARGET ; TRANSGENIC MICE ; LUNG-CANCER ; IN-VIVO ; EXPRESSION ; PROMOTER ; ADENOVIRUS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000243525900011 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1781]  |
| 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 | Li, BH,Fan, JK,Liu, XR,et al. Suppression of colorectal tumor growth by regulated survivin targeting[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2006,84(12):1077-1086. |
| APA | Li, BH.,Fan, JK.,Liu, XR.,Qi, R.,Bo, LN.,...&Liu, XY.(2006).Suppression of colorectal tumor growth by regulated survivin targeting.JOURNAL OF MOLECULAR MEDICINE-JMM,84(12),1077-1086. |
| MLA | Li, BH,et al."Suppression of colorectal tumor growth by regulated survivin targeting".JOURNAL OF MOLECULAR MEDICINE-JMM 84.12(2006):1077-1086. |
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