Tumor-targeting prodrug-activating bacteria for cancer therapy

C. M. Cheng, Y. L. Lu, K. H. Chuang, W. C. Hung, J. Shiea, Y. C. Su, C. H. Kao, B. M. Chen, S. Roffler, T. L. Cheng

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53 引文 斯高帕斯(Scopus)

摘要

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. β-glucuronidase and the luxCDABE gene cluster were expressed in the DH5α strain of Escherichia coli to generate DH5α-lux/βG. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for βG activity, we found that DH5α-lux/βG preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and βG activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5α-lux/βG, 9AC or 9ACG treatment, combined systemic administration of DH5α-lux/βG followed by 9ACG prodrug treatment significantly (P<0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.

原文英語
頁(從 - 到)393-401
頁數9
期刊Cancer Gene Therapy
15
發行號6
DOIs
出版狀態已發佈 - 六月 2008
對外發佈

ASJC Scopus subject areas

  • 分子醫學
  • 分子生物學
  • 癌症研究

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