Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model
文献类型：期刊论文
| 作者 | Lei, W; Liu, HB; Wang, SB; Zhou, XM; Zheng, SD; Guo, KN; Ma, BY; Xia, YL; Tan, WS; Liu, XY |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013 |
| 卷号 | 34期号:4页码:531-540 |
| 关键词 | lung cancer tumor suppressor in lung cancer-1 oncolytic adenovirus survivin apoptosis caspase signaling pathway tumor xenograft model |
| 通讯作者 | Wang, YG (reprint author), Zhejiang Sci Tech Univ, Coll Biol Sci, Xinyuan Inst Med & Biotechnol, Hangzhou 310018, Zhejiang, Peoples R China.,wangyigang43@163.com |
| 英文摘要 | Aim: The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. Methods: The recombinant virus Ad.sp-E1A((Delta 24))-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad.sp-E1A((Delta 24)) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad.sp-E1A((Delta 24))-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. Results: Infection of A549 lung cancer cells with Ad.sp-E1A((Delta 24))-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad.sp-E1A((Delta 24))-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad.sp-E1A((Delta 24))-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad.sp-E1A((Delta 24))-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad.sp-E1A((Delta 24))-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. Conclusion: The oncolytic adenovirus Ad.sp-E1A((Delta 24))-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer. |
| 学科主题 | Chemistry; Pharmacology & Pharmacy |
| 类目[WOS] | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| 关键词[WOS] | ANTI-APOPTOSIS GENE ; PROMOTER METHYLATION ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; DNA METHYLATION ; GASTRIC-CANCER ; CELL-ADHESION ; SURVIVIN ; EXPRESSION ; THERAPY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000317106600012 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/379]  |
| 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 | Lei, W,Liu, HB,Wang, SB,et al. Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model[J]. ACTA PHARMACOLOGICA SINICA,2013,34(4):531-540. |
| APA | Lei, W.,Liu, HB.,Wang, SB.,Zhou, XM.,Zheng, SD.,...&Wang, YG.(2013).Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model.ACTA PHARMACOLOGICA SINICA,34(4),531-540. |
| MLA | Lei, W,et al."Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model".ACTA PHARMACOLOGICA SINICA 34.4(2013):531-540. |
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