Expressing cytotoxic compounds in Escherichia coli Nissle 1917 for tumor-targeting therapy
Expressing cytotoxic compounds in Escherichia coli Nissle 1917 for tumor-targeting therapy
复制标题
在大肠杆菌 Nissle 1917 中表达细胞毒性化合物用于肿瘤靶向治疗。
DOI：
10.1016/j.resmic.2018.11.001
复制
发表时间：
2019-03-01
影响因子：
2.6
通讯作者：
Zhang, Youming
中科院分区：
文献类型：
--
作者：
Li, Ruijuan;Helbig, Linda;Zhang, Youming
异常血管以及缺氧和坏死区域是实体瘤的常见特征，并且与恶性表型和治疗抗性相关。某些专性或兼性厌氧菌在体内具有在实体瘤内定植和增殖的固有能力。大肠杆菌Nissle 1917（EcN）是欧洲市场上的一种非致病性益生菌，已知其能在实体瘤的存活区域和坏死区域之间的界面选择性增殖。本研究的目的是利用基因工程改造的EcN建立一种肿瘤靶向治疗系统，用于靶向递送细胞毒性化合物，包括大肠杆菌素、滑菌素和发光酰胺。将这些细胞毒性化合物的生物合成基因簇引入EcN，并在所得重组EcN菌株中检测到相应的化合物。重组EcN在体外和体内均显示出显著的细胞毒活性，并显著抑制肿瘤生长。总之，本研究证实了EcN有效的肿瘤靶向定植，并展示了其作为一种新的肿瘤靶向治疗系统在肿瘤特异性递送细胞毒性化合物方面的潜力。（C）2018由爱思唯尔马松公司代表巴斯德研究所出版。
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.