NF-kappaB activity blockade impairs the angiogenic potential of human pancreatic cancer cells

Int J Cancer. 2004 Jan 10;108(2):181-8. doi: 10.1002/ijc.11562.


The effect of blockade of NF-kappaB activity on human pancreatic cancer angiogenesis was determined in an orthotopic xenograft model. Highly metastatic L3.3 human pancreatic cancer cells, which expressed an elevated level of constitutive NF-kappaB activity, were transfected with a mutated IkappaBalpha (IkappaBalphaM). After implantation in the pancreas of nude mice, parental (L3.3) and control vector-transfected (L3.3-Neo) cells produced rapidly growing tumors and liver metastases, whereas IkappaBalphaM-transfected (L3.3-IkappaBalphaM) cells had decreased tumorigenicity and metastatic potential. NF-kappaB signaling blockade significantly inhibited the in vitro and in vivo expression of the major proangiogenic molecules vascular endothelial growth factor and interleukin-8 and decreased tumor vascular formation. These events were correlated with retarded tumor growth and suppression of metastasis. Collectively, these data suggest that suppression of tumorigenicity and metastasis by NF-kappaB blockade is due to impaired angiogenic potential of tumor cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutation
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / physiology
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / prevention & control
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / prevention & control
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Promoter Regions, Genetic
  • Signal Transduction / physiology
  • Transfection
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays


  • I-kappa B Proteins
  • Interleukin-8
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Vascular Endothelial Growth Factor A
  • NF-KappaB Inhibitor alpha