title: Lentivirus-AIMP2-DX2 shRNA suppresses cell proliferation by regulating Akt1 signaling pathway in the lungs of AIMP2⁺/⁻ mice.
abstract: BACKGROUND
  The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer numerous advantages over invasive modes of delivery.
  
  
  METHODS
  The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks.
  
  
  CONCLUSIONS
  The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Soon-Kyung
authors.initials: SK
authors.lastname: Hwang
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D016086:Lentivirus / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D015398:Signal Transduction
chemical_list: D000336:Aerosols; D034741:RNA, Small Interfering; C474321:aminoacyl-tRNA synthetase-associated protein p38; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D000604:Amino Acyl-tRNA Synthetases