期刊
CELL CYCLE
卷 13, 期 24, 页码 3958-3963出版社
LANDES BIOSCIENCE
DOI: 10.4161/15384101.2014.964115
关键词
cell cycle; chemotherapy; decoy; FUCCI; GFP; RFP; imaging; S; typhimurium A1-R; tumor-targeting bacteria; FUCCI; fluorescence ubiquitination-based cell cycle indicator; S; typhimurium; Salmonella typhimurium
类别
资金
- National Cancer Institute [CA132971]
Quiescent cancer cells are resistant to cytotoxic agents which target only proliferating cancer cells. Time-lapse imaging demonstrated that tumor-targeting Salmonella typhimurium A1-R (A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G(0)/G(1) to S/G(2)/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. A1-R infection of FUCCI-expressing subcutaneous tumors growing in nude mice also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G(0)/G(1) to S/G(2)/M, thereby making them sensitive to cytotoxic agents. The combination of A1-R and cisplatinum or paclitaxel reduced tumor size compared with A1-R monotherapy or cisplatinum or paclitaxel alone. The results of this study demonstrate that A1-R can decoy quiescent cancer cells to cycle to S/G(2)/M and sensitize them to cytotoxic chemotherapy. These results suggest a new paradigm of bacterial-decoy chemotherapy of cancer.
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