title: Gene transfer of inhibitor kappaB in human lung cancer cell line NCI-H460 inhibits tumorigenesis and angiogenesis in vivo.
abstract: BACKGROUND
  Nuclear factor kappaB (NFkappaB) is an inducible and ubiquitously expressed transcription factor which is involved in cell survival, differentiation and growth and, thus, has also been implicated in tumor formation and development. Research on the effect of NFkappaB in inhibiting cancer cell growth, however, remains controversial.
  
  
  METHODS
  We investigated the effects of overexpressed IkappaBalpha on the proliferation of the human lung cancer cell line H460 in vitro and in vivo using IkappaBalpha-expressing adenovirus.
  
  
  RESULTS
  The results suggested that the infection of AdIkappaBalpha blocked NFkappaB activity in H460 cells and significantly inhibited cell proliferation by inducing apoptosis. An in vivo study showed the tumor incidence to be significantly lower in mice implanted with H460 cells infected with AdIkappaBa. For established H460 tumor, the intratumoral injection of AdIkappaBalpha also inhibited the tumor growth due to both a blockade of the NFkappaB activity and an inhibition of the VEGF expression.
  
  
  CONCLUSIONS
  Adenovirus-mediated IkappaBalpha gene transfer is a promising cancer treatment strategy.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoshima
authors.forename: Junji
authors.initials: J
authors.lastname: Uchino
authors.forename: Akiko
authors.initials: A
authors.lastname: Harada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Minami
authors.forename: Taishi
authors.initials: T
authors.lastname: Harada
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D042461:Vascular Endothelial Growth Factor A; D000072000:NF-KappaB Inhibitor alpha; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases