Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.
Cancer Gene Ther. 2012 May;19(5):345-51. doi: 10.1038/cgt.2012.7. Epub 2012 Mar 9.
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.
我们之前构建了一个人工启动子，该启动子可响应 X 射线照射在前列腺癌细胞系 LNCap 中被激活。我们检测了一些抗癌药物，以观察它们是否可以刺激启动子的活性。结果发现，阿霉素（Dox）处理转染了该启动子控制下的荧光素酶基因的 LNCap 细胞，可使荧光素酶活性呈剂量依赖性增强，表明该启动子可被 Dox 调控。当将荧光素酶基因替换为 fcy::fur 基因时，其产物可促进将 5-氟胞嘧啶转化为高度毒性的 5-氟尿嘧啶，阿霉素刺激了该基因产物的表达，从而在存在 5-氟胞嘧啶的情况下促进了细胞杀伤作用。这些结果表明，用抗癌药物控制治疗性基因表达可能会导致更有效的癌症治疗，而副作用的风险更小。
