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Adenoviral vector transduction of the human deoxycytidine kinase gene enhances the cytotoxic and radiosensitizing effect of gemcitabine on experimental gliomas

Cancer Gene Therapy volume 15, pages 154–164 (2008)Cite this article

Abstract

The aim of this work was to improve the cytotoxic and radiosensitizing effects of gemcitabine using a gene-directed enzyme prodrug therapy approach. Murine Gl261, rat C6 and human U373 glioma cell lines were transduced with an adenoviral vector encoding the human deoxycytidine kinase gene (Ad-HudCK). Intracranial tumors were established in C57BL/6 mice and Wistar rats using either wild-type or Ad-HudCK-transduced Gl261 and C6 glioma cells. In vitro growing cells and established tumors were treated with gemcitabine and irradiation either alone or in combination. Deoxycytidine kinase overexpression substantially increased both the toxic and radiosensitizing effects of gemcitabine in each cell line, but the enhancement rate varied: it was mild in the Gl261 cells and much stronger in the C6 and U373 cells. In vivo experiments showed a mild radiosensitizing effect of dCK overexpression both in the Gl261 and C6 models. The combination of dCK overexpression, gemcitabine treatment and irradiation improved the survival rate of C6 bearing rats significantly. In conclusion, overexpression of the dCK gene can improve the cytotoxic and radiosensitizing effect of gemcitabine both in vitro and in vivo in a tumor-specific manner.

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Acknowledgements

We appreciate the expert technical assistance of Erzsébet Fekete, Éva Tölcsér and Rita Lökös. This work was supported by the following Hungarian grants: ETT 234/2006 and OTKA F034775 to KL, OTKA F46330 to SD, ETT-413/2006, OTKA T-047034, and GVOP-3.1.1.-2004-05-0389/3.0 to GS and OTKA T-046730 to TS.

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Author notes

  1. T Szatmári and G Huszty: These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Molecular and Tumor Radiobiology, ‘Frédéric Joliot-Curie’ National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary

    T Szatmári, G Huszty, S Désaknai, G Sáfrány & K Lumniczky

  2. Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

    T Spasokoukotskaja, M Sasvári-Székely & M Staub

  3. Department of Oncotherapy, University of Pécs, Pécs, Hungary

    O Ésik

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Correspondence to K Lumniczky.

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Szatmári, T., Huszty, G., Désaknai, S. et al. Adenoviral vector transduction of the human deoxycytidine kinase gene enhances the cytotoxic and radiosensitizing effect of gemcitabine on experimental gliomas. Cancer Gene Ther 15, 154–164 (2008). https://doi.org/10.1038/sj.cgt.7701115

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