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Development of Oxytolerant Salmonella typhimurium Using Radiation Mutation Technology (RMT) for Cancer Therapy

Title
Development of Oxytolerant Salmonella typhimurium Using Radiation Mutation Technology (RMT) for Cancer Therapy
Authors
Gao S.Jung J.-H.Lin S.-M.Jang A.-Y.Zhi Y.Bum Ahn K.Ji H.-J.Hyang Lim J.Guo H.Choy H.E.Lim S.Seo H.S.
Ewha Authors
임재향
SCOPUS Author ID
임재향scopus
Issue Date
2020
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
Scientific Reports vol. 10, no. 1
Publisher
Nature Research
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
A critical limitation of Salmonella typhimurium (S. typhimurium) as an anti-cancer agent is the loss of their invasive or replicative activities, which results in no or less delivery of anti-cancer agents inside cancer cells in cancer therapy. Here we developed an oxytolerant attenuated Salmonella strain (KST0650) from the parental KST0649 (ΔptsIΔcrr) strain using radiation mutation technology (RMT). The oxytolerant KST0650 strain possessed 20-times higher replication activity in CT26 cancer cells and was less virulent than KST0649. Furthermore, KST0650 migrated effectively into tumor tissues in mice. KST0650 was further equipped with a plasmid harboring a spliced form of the intracellular pro-apoptotic protein sATF6, and the expression of sATF6 was controlled by the radiation-inducible recN promoter. The new strain was named as KST0652, in which sATF6 protein expression was induced in response to radiation in a dose-dependent manner. This strain was effectively delivered inside cancer cells and tumor tissues via the Salmonella type III secretion system (T3SS). In addition, combination treatment with KST0652 and radiation showed a synergistic anti-tumor effect in murine tumor model with complete inhibition of tumor growth and protection against death. In conclusion, we showed that RMT can be used to effectively develop an anti-tumor Salmonella strain for delivering anti-cancer agents inside tumors. © 2020, The Author(s).
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DOI
10.1038/s41598-020-60396-6
Appears in Collections:
의과대학 > 의학과 > Journal papers
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