Gene transfer of inhibitor kappaB in human lung cancer cell line NCI-H460 inhibits tumorigenesis and angiogenesis in vivo

Anticancer Res. 2005 Jan-Feb;25(1A):69-77.

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.

Materials and 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.

Conclusion: Adenovirus-mediated IkappaBalpha gene transfer is a promising cancer treatment strategy.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / genetics
  • Caspase 3
  • Caspases / metabolism
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Genetic Therapy / methods*
  • Humans
  • I-kappa B Proteins / biosynthesis
  • I-kappa B Proteins / genetics*
  • Immunohistochemistry
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Vascular Endothelial Growth Factor A
  • NF-KappaB Inhibitor alpha
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases