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An artificially constructed radiation-responsive promoter is activated by doxorubicin

Cancer Gene Therapy volume 19, pages 345–351 (2012)Cite this article

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Abstract

We previously developed an artificially constructed promoter that was activated in response to X-ray irradiation in LNCap, a prostate cancer cell line. Anticancer drugs were examined to see whether some of them could stimulate the activity of the promoter. It was found that doxorubicin (Dox) treatment to LNCap transfected with a gene cassette of the luciferase gene under control of the promoter-enhanced luciferase activity in a dose-dependent manner, indicating that the promoter could be controlled by Dox. When the luciferase gene was replaced with the fcy::fur gene whose product facilitates conversion of 5-fluorocytosine into 5-fluorouracil that is highly toxic, Dox stimulated the expression of the gene product, resulting in facilitation of cell killing effect in the presence of 5-fluorocytosine. These results suggest that therapeutic gene expression controlled with an anticancer drug may lead to a more effective cancer therapy with less hazardous side effects.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research (C) (21500403) and for Young Scientist (B) (20377253 and 23791746) from Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan

    R Ogawa, N Doi & Q L Zhao

  2. Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan

    A Morii & A Watanabe

  3. Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan

    Z-G Cui

  4. School of Allied Health Sciences, Kitasato University, Sagamihara, Japan

    G Kagiya

  5. Department of Anatomy, School of Medicine, Fukuoka University, Fukuoka, Japan

    L B Feril Jr

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  1. R Ogawa
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  2. A Morii
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  3. A Watanabe
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  4. Z-G Cui
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  5. G Kagiya
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  6. N Doi
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  7. Q L Zhao
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  8. L B Feril Jr
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Correspondence to R Ogawa.

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Ogawa, R., Morii, A., Watanabe, A. et al. An artificially constructed radiation-responsive promoter is activated by doxorubicin. Cancer Gene Ther 19, 345–351 (2012). https://doi.org/10.1038/cgt.2012.7

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  • DOI: https://doi.org/10.1038/cgt.2012.7

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