title: Attenuated Salmonella typhimurium carrying TRAIL and VP3 genes inhibits the growth of gastric cancer cells in vitro and in vivo.
abstract: BACKGROUND
  Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and apoptin (VP3) of chicken anemia virus can selectively induce apoptosis in human tumor cell lines by two different pathways. Salmonella not only delivers functional genes to mammalian cells but also possesses antitumor activity and therefore could be adopted as a novel vector for anticancer therapy.
  
  
  METHODS
  TRAIL and VP3 genes were cloned into a pBudCE4.1 vector and delivered by attenuated Salmonella typhimurium into gastric cancer cells, and their expression and antitumor effects in nude mice were monitored by Western blot, fluorescence microscopy, MTT assay, TUNEL staining, and immunohistochemistry.
  
  
  RESULTS
  pBud-VP3 and pBud-TRAIL-VP3 plasmids were constructed to express TRAIL and apoptin in gastric cancer cells, leading to inhibition of cancer cell proliferation after 48 hours (P < 0.05). TRAIL and VP3 genes in pBudCE4.1 vector were also successfully delivered by attenuated S. typhimurium into gastric cancer cells in vivo, in which both TRAIL and apoptin were expressed. In vivo data indicated that S. typhimurium carring pBud-TRAIL-VP3 induced significant cell growth inhibition and tumor regression (P < 0.05). Moreover, expression of TRAIL and apoptin increased the expression of caspase-3 and caspase-9, resulting in enhanced apoptosis.
  
  
  CONCLUSIONS
  Delivery of TRAIL and VP3 genes by attenuated S. typhimurium can significantly inhibit the growth of gastric cancer cells in vitro and in vivo.
authors.affiliation: Department of Gastroenterology, Chongqing Medical University, Chongqing, China.
authors.forename: Hong-Dan
authors.initials: HD
authors.lastname: Cao
authors.forename: Yin-Xue
authors.initials: YX
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Lü
authors.forename: Shao-Ning
authors.initials: SN
authors.lastname: Liu
authors.forename: Pi-Long
authors.initials: PL
authors.lastname: Wang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Tao
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Ting-Xiu
authors.initials: TX
authors.lastname: Xiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000235:genetics*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D036022:Capsid Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C091717:VP3 protein, Chicken anemia virus; D053148:Caspase 3; D053453:Caspase 9