論文 - 詳細
| RRC ID | 38532 |
|---|---|
| 著者 | Cao X, Yang M, Wei RC, Zeng Y, Gu JF, Huang WD, Yang DQ, Li HL, Ding M, Wei N, Zhang KJ, Xu B, Liu XR, Qian QJ, Liu XY. |
| タイトル | Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated oncolytic adenovirus armed with TRAIL gene. |
| ジャーナル | Gene Ther |
| Abstract |
Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated Ad·AFP·E1A·E1B (Δ55) (Ad·AFP·D55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/α-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. Ad·AFP·D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into Ad·AFP·D55. Ad·AFP·D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad·AFP·D55-TRAIL can induce both autophagy owing to the Ad·AFP·D55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, Ad·AFP·D55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis. |
| 巻・号 | 18(8) |
| ページ | 765-77 |
| 公開日 | 2011-8-1 |
| DOI | 10.1038/gt.2011.16 |
| PII | gt201116 |
| PMID | 21412282 |
| MeSH | Adenoviridae / genetics* Animals Apoptosis Autophagy Bystander Effect Carcinoma, Hepatocellular / therapy* Cell Line, Tumor Genetic Therapy / methods* Genetic Vectors Humans Liver Neoplasms / therapy* Mice Mice, Nude Oncolytic Virotherapy / methods* Oncolytic Viruses / genetics* TNF-Related Apoptosis-Inducing Ligand / genetics* alpha-Fetoproteins / genetics |
| IF | 4.128 |
| 引用数 | 29 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) HuH-6(RCB1367) |