Antitumor effect of a novel adeno-associated virus vector targeting to telomerase activity in tumor cells.
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-beta (hIFN-beta) gene under the control of hTERT promoter (AAV-hTERT-hIFN-beta) and investigated its antitumor effect against various human cancer cells in vitro. AAV-hTERT-hIFN-beta displayed cancer-specific hIFN-beta expression and cytotoxicity. The cytotoxic ratio was positively correlated with the time length of infection. AAV-hTERT-hIFN-beta-mediated apoptotic morphology was observed by transmission electron microscopy. Flow cytometry assay also revealed that the cytotoxicity of AAV-hTERT-hIFN-beta 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.
Wang
Yi-Gang
YG
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Wang
Jin-Hui
JH
Zhang
Yan-Hong
YH
Gu
Qing
Q
Liu
Xin-Yuan
XY
D017209:Apoptosis; D002460:Cell Line; D004268:DNA-Binding Proteins; D000229:Dependovirus / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006801:Humans; D008854:Microscopy, Electron; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019098:Telomerase