Antitumor Effect of a Novel Adeno-associated Virus Vector Targeting to Telomerase Activity in Tumor Cells

摘要

Telomerase activity is a wide tumor marker. Human telomerase reverse transcriptase (hTERT),the catalytic subunit of the telomerase, is transcriptionally upregulated exclusively in about 90% of cancer cells. In this study, we constructed a novel adeno-associated virus (AAV) vector containing the human interferon-β (hIFN-β) gene under the control of hTERT promoter (AAV-hTERT-hIFN-β) and investigated its antitumor effect against various human cancer cells in vitro. AAV-hTERT-hIFN-β displayed cancer-specific hIFN-β expression and cytotoxicity. The cytotoxic ratio was positively correlated with the time length of infection. AAV-hTERT-hIFN-β-mediated apoptotic morphology was observed by transmission electron microscopy. Flow cytometry assay also revealed that the cytotoxicity of AAV-hTERT-hIFN-β was mainly an apoptotic process. These data indicate that AAV in combination with hTERT-mediated therapeutic gene expression may open new possibilities for long-lasting and targeting gene therapy of varieties of cancers.