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Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC.
- Source :
-
Cancer Gene Therapy . Jun2012, Vol. 19 Issue 6, p393-401. 9p. 2 Charts, 6 Graphs. - Publication Year :
- 2012
-
Abstract
- The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09291903
- Volume :
- 19
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 75275249
- Full Text :
- https://doi.org/10.1038/cgt.2012.12