Abstract
Aim:
To examine whether attenuated Salmonella typhimurium (S typhimurium) could be used as an anti-cancer agent or a tumor-targeting vehicle for delivering shRNA-expressing pDNA into cancer cells in a mouse tumor model.
Methods:
Mouse bladder transitional cancer cell line (BTT-T739) expressing GFP was used, in which the GFP expression level served as an indicator of RNA interference (RNAi). BTT-T739-GFP tumor-bearing mice (4–6 weeks) were treated with S typhimurium carrying plasmids encoding shRNA against gfp or scrambled shRNA. The mRNA and protein expression levels of GFP were assessed 5 d after the bacteria administration, and the antitumor effects of S typhimurium were evaluated.
Results:
In BTT-T739-GFP tumor-bearing mice, S typhimurium (1×109 cfu, po) preferentially accumulated within tumors for as long as 40 d, and formed a tumor-to-normal tissue ratio that exceeded 1000/1. S typhimurium carrying plasmids encoding shRNA against gfp inhibited the expression of GFP in tumor cells by 73.4%. Orally delivered S typhimurium significantly delayed tumor growth and prolonged the survival of tumor-bearing mice.
Conclusion:
This study demonstrates that attenuated S typhimurium can be used for both delivering shRNA-expressing vectors into tumor cells and eliciting RNAi, thus exerting anti-tumor activity, which may represent a new strategy for the treatment of solid tumors.
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Acknowledgements
We thank Fudan University State Key Laboratory of Genetic Engineering for technical support and Su-qin SHEN for her excellent technical assistance. We thank Prof Qian WANG and Feng HUANG for their generous offer of the cell line. We also thank Xiao WANG, Lu-biao HUANG, Meng-ning ZHOU, and Gao-feng LIU for their kind support and helpful suggestions regarding this project.
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Yang, N., Li, Sh., Lü, Yz. et al. Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors. Acta Pharmacol Sin 32, 368–374 (2011). https://doi.org/10.1038/aps.2010.224
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DOI: https://doi.org/10.1038/aps.2010.224
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