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

文献类型： 外文期刊

第一作者： Gao, Shuang

作者： Gao, Shuang;Jung, Jong-Hyun;Lin, Shun-Mei;Jang, A-Yeung;Zhi, Yong;Ahn, Ki Bum;Ji, Hyun-Jung;Lim, Sangyong;Seo, Ho Seong;Gao, Shuang;Lin, Shun-Mei;Choy, Hyon E.;Jung, Jong-Hyun;Zhi, Yong;Lim, Sangyong;Seo, Ho Seong;Jang, A-Yeung;Lim, Jae Hyang;Guo, Huichen

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2020 年 10 卷 1 期

页码：

收录情况： SCI

摘要： 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 (Delta ptsI Delta crr) 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 proapoptotic 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.

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