期刊
RESEARCH IN MICROBIOLOGY
卷 170, 期 2, 页码 74-79出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.resmic.2018.11.001
关键词
Escherichia coli Nissle 1917 (EcN); Tumor-targeting therapy; Biosynthetic gene cluster; Cytotoxic compounds; Solid tumors
类别
资金
- National Natural Science Foundation of China [81502962, 31670097]
- China Postdoctoral Science Foundation [2015M572017]
- Major Project of Science and Technology of Shandong Province [2015ZDJS04001]
- Key Research and Development Program of Shandong Province [2015GSF12101]
- International Science & Technology Cooperation Program of China [2015DFE32850]
Abnormal blood vessels and hypoxic and necrotic regions are common features of solid tumors and related to the malignant phenotype and therapy resistance. Certain obligate or facultative anaerobic bacteria exhibit inherent ability to colonize and proliferate within solid tumors in vivo. Escherichia coli Nissle 1917 (EcN), a non-pathogenic probiotic in European markets, has been known to proliferate selectively in the interface between the viable and necrotic regions of solid tumors. The objective of this study was to establish a tumor-targeting therapy system using the genetically engineered EcN for targeted delivery of cytotoxic compounds, including colibactin, glidobactin and luminmide. Biosynthetic gene clusters of these cytotoxic compounds were introduced into EcN and the corresponding compounds were detected in the resultant recombinant EcN strains. The recombinant EcN showed significant cytotoxic activity in vitro and in vivo as well, and significantly suppressed the tumor growth. Together, this study confirmed efficient tumor-targeting colonization of EcN and demonstrated its potentiality in the tumor-specific delivery of cytotoxic compounds as a new tumor-targeting therapy system. (C) 2018 Published by Elsevier Masson SAS on behalf of Institut Pasteur.
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