文献类型：期刊文献

英文题名：Potent antitumor effect of TRAIL mediated by a novel adeno-associated viral vector targeting to telomerase activity for human hepatocellular carcinoma

作者：Wang, Yigang[1,2];Huang, Fang[2];Cai, Haibo[1];Zhong, Suyang[2];Liu, Xinyuan[2,3];Tan, Wen-Song[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zheijiang Sci Tech Univ, Coll Life Sci, Xin Yuan Inst Med & Biotechnol, Hangzhou 310018, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China

年份：2008

卷号：10

期号：5

起止页码：518

外文期刊名：JOURNAL OF GENE MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000256244900004)】；

语种：英文

外文关键词：adeno-associated virus; hTERT promoter; TRAIL; antitumor efficacy

摘要：Background Adeno-associated virus (AAV) has rapidly become a promising gene delivery vehicle for its excellent advantages of low pathogenicity and long-term gene expression. However, lack of tissue specificity caused low efficiency of AAV transfer to target cells. The promoter of human telomerase reverse transcriptase (hTERT) has been implicated in mediating gene expression in cancer cells as hTERT is transcriptionally upregulated in most cancer cells. Thereby, the hTERT promoter becomes a good candidate to enhance the targeting efficiency of AAV in cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. it remains to be determined whether the hTERT promoter can efficiently mediate TRAIL gene therapy in cancer cells using AAV vector. Methods A novel AAV vector containing the TRAIL gene under the control of the hTERT promoter (AAV-hTERT-TRAIL) was generated. The specific expression of hTERT-controlled genes was evaluated in cell lines. The antitumor efficacy of AAV-hTERT-TRAIL was assessed in tumor cell lines and human hepatocellular carcinoma xenograft mouse model. Results TRAIL expression was observed in tumor cells infected with AAV-hTERT-TRAIL at both the protein and mRNA level. AAV-hTERT-TRAIL displayed cancer-specific cytotoxicity and induced tumor cell apoptosis. Moreover, in animal experiments, intratumoral administration of AAV-hTERT-TRAIL significantly suppressed the growth of xenograft tumors and resulted in tumor cell death. Conclusions AAVs in combination with hTERT-mediated therapeutic gene expression provide a promising targeting approach for developing effective therapy for human cancers. These data suggest that AAV-hTERT-TRAIL is a potent therapeutic agent for cancer therapy. Copyright (c) 2008 John Wiley & Sons, Ltd.