Abstract |
Adeno-associated virus (AAV) is a non-pathogenic virus with a single-strand DNA genome. AAV vectors have several unique properties suited for gene therapy applications. However, an obstacle to their application is a low efficiency of transgene expression, mainly due to a limited second-strand synthesis. Previously, we reported that gamma-rays enhanced the transduction efficiency and cytocidal effect of AAV vector harboring the herpes simplex virus- thymidine kinase (AAVtk) and ganciclovir (GCV) system. In the present study, we investigated whether topoisomerase inhibitors ( etoposide and camptothecin) enhance the AAV vector-mediated transgene expression and the killing effect by AAVtk/GCV system. The enhancement of transgene expression was observed in a concentration-dependent manner on human laryngeal carcinoma cells (HEp-2 cells) and HeLa cells. Southern analysis confirmed that etoposide enhanced the double-strand synthesis of the AAV vector genome in HEp-2 cells and HeLa cells. The cells were efficiently killed by AAVtk/GCV system, as expected. More importantly, both etoposide and camptothecin augmented the cytocidal effect of the AAVtk/GCV system. These findings suggest that the combination of AAV-mediated suicide gene therapy and treatment with topoisomerase inhibitors may have synergistic therapeutic effects in the treatment of cancers.
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Authors | Takeharu Kanazawa, Hiroaki Mizukami, Hiroshi Nishino, Takashi Okada, Yutaka Hanazono, Akihiro Kume, Ken Kitamura, Keiichi Ichimura, Keiya Ozawa |
Journal | International journal of oncology
(Int J Oncol)
Vol. 25
Issue 3
Pg. 729-35
(Sep 2004)
ISSN: 1019-6439 [Print] Greece |
PMID | 15289876
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Enzyme Inhibitors
- Topoisomerase I Inhibitors
- Etoposide
- Thymidine Kinase
- Ganciclovir
- Camptothecin
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Topics |
- Antineoplastic Agents, Phytogenic
(therapeutic use)
- Camptothecin
(pharmacology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Dependovirus
(drug effects, genetics)
- Enzyme Inhibitors
(therapeutic use)
- Etoposide
(pharmacology)
- Ganciclovir
(therapeutic use)
- Gene Expression
- Genes, Transgenic, Suicide
- Genetic Therapy
- Genetic Vectors
(genetics)
- Head and Neck Neoplasms
(drug therapy, therapy)
- Humans
- Thymidine Kinase
(genetics, metabolism)
- Topoisomerase I Inhibitors
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