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Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors

  
@article{APS6713,
	author = {Nan Yang and Sheng-hua Li and Yun-zhe Lü and Li-shan Chen and Da-ming Ren},
	title = {Attenuated  Salmonella typhimurium  carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors},
	journal = {Acta Pharmacologica Sinica},
	volume = {32},
	number = {3},
	year = {2016},
	keywords = {},
	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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/6713}
}