An artificially constructed radiation-responsive promoter is activated by doxorubicin.

R Ogawa, A Morii, A Watanabe, Z-G Cui, G Kagiya, N Doi, Q L Zhao, L B Feril

Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan. ogawa@med.u-toyama.ac.jp

Cancer gene therapy 2012 May

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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.

Citation

R Ogawa, A Morii, A Watanabe, Z-G Cui, G Kagiya, N Doi, Q L Zhao, L B Feril. An artificially constructed radiation-responsive promoter is activated by doxorubicin. Cancer gene therapy. 2012 May;19(5):345-51