HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a Cancer Targeting Gene-Viro-Therapy strategy
文献类型：期刊论文
| 作者 | Xu, HN; Huang, WD; Cai, Y; Ding, M; Gu, JF; Wei, N; Sun, LY; Cao, X; Li, HG; Zhang, KJ |
| 刊名 | MOLECULAR CANCER
 |
| 出版日期 | 2011 |
| 卷号 | 10期号:1页码:133-133 |
| 关键词 | liver cancer quadruple regulated adenovirus HCCS1 mitochondrial apoptosis pathway |
| 通讯作者 | Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,xyliu@sibs.ac.cn |
| 英文摘要 | Background: In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus. Accordingly, in this study, we deleted 24 bp in E1A (bp924-bp947) and the entirety of E1B, including those genes encoding E1B 55kDa and E1B19kDa. We used the survivin promoter (SP) to control E1A in order to construct a new adenovirus vector named Ad. SP. E1A(Delta 24).Delta E1B (briefly Ad.SPDD). HCCS1 (hepatocellular carcinoma suppressor 1) is a novel tumor suppressor gene that is able to specifically induce apoptosis in cancer cells. The expression cassette AFP-HCCS1-WPRE-SV40 was inserted into Ad.SPDD to form Ad.SPDD-HCCS1, enabling us to improve the safety and efficacy of oncolytic-mediated gene therapy for liver cancer. Results: Ad.SPDD showed a decreased viral yield and less toxicity in normal cells but enhanced toxicity in liver cancer cells, compared with the cancer-specific adenovirus ZD55 (E1B55K deletion). Ad.SPDD-HCCS1 exhibited a potent anti-liver-cancer ability and decreased toxicity in vitro. Ad.SPDD-HCCS1 also showed a measurable capacity to inhibit Huh-7 xenograft tumor growth on nude mice. The underlying mechanism of Ad.SPDD-HCCS1-induced liver cancer cell death was found to be via the mitochondrial apoptosis pathway. Conclusions: These results demonstrate that Ad.SPDD-HCCS1 was able to elicit reduced toxicity and enhanced efficacy both in vitro and in vivo compared to a previously constructed oncolytic adenovirus. Ad.SPDD-HCCS1 could be a promising candidate for liver cancer therapy. |
| 学科主题 | Biochemistry & Molecular Biology; Oncology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Oncology |
| 关键词[WOS] | INCREASES ANTITUMOR-ACTIVITY ; APOPTOSIS-INDUCING LIGAND ; HEPATOCELLULAR-CARCINOMA ; IN-VIVO ; ALPHA-FETOPROTEIN ; TUMOR-CELLS ; EXPRESSION ; HEPATITIS ; MUTANT ; ERADICATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000297273200001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/905]  |
| 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 | Xu, HN,Huang, WD,Cai, Y,et al. HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a Cancer Targeting Gene-Viro-Therapy strategy[J]. MOLECULAR CANCER,2011,10(1):133-133. |
| APA | Xu, HN.,Huang, WD.,Cai, Y.,Ding, M.,Gu, JF.,...&Liu, XY.(2011).HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a Cancer Targeting Gene-Viro-Therapy strategy.MOLECULAR CANCER,10(1),133-133. |
| MLA | Xu, HN,et al."HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a Cancer Targeting Gene-Viro-Therapy strategy".MOLECULAR CANCER 10.1(2011):133-133. |
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