title: Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC.
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.
authors.affiliation: Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: B
authors.initials: B
authors.lastname: Guo
authors.forename: H
authors.initials: H
authors.lastname: Jia
authors.forename: K
authors.initials: K
authors.lastname: Ji
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Meng
authors.forename: D V
authors.initials: DV
authors.lastname: Kalvakolanu
authors.forename: D J
authors.initials: DJ
authors.lastname: Kopecko
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D059585:G1 Phase Cell Cycle Checkpoints; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010957:Plasmids; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology; D047368:Tumor Burden
chemical_list: D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D049452:Green Fluorescent Proteins