Nuclear factor kappa B activation is a potential target for preventing pancreatic carcinoma by aspirin

Cancer. 2005 Jun 15;103(12):2485-90. doi: 10.1002/cncr.21075.


Background: Pancreatic carcinoma exhibits a unique genetic profile of mutations that may play key roles in its progression to malignant phenotypes. Constitutive activation of transcription factor nuclear factor kappa B (NF-kappaB) is a frequent molecular alteration in pancreatic carcinoma, suggesting a possible link between inflammation and cancer. The aims of the current study were to determine the effects of aspirin on pancreatic carcinoma prevention and to reveal a possible mechanism of aspirin-mediated cancer chemoprevention.

Methods: An orthotopic mouse model with human pancreatic carcinoma cell lines PANC-1, PANC-1/Puro, and PANC-1/IkappaBalphaM was used to study the inhibitory effects of aspirin on pancreatic tumor formation.

Results: Aspirin inhibited constitutive NF-kappaB activity in culture and, in turn, decreased the expression of the NF-kappaB downstream target gene, Cox-2, in PANC-1 or PANC-1/Puro cells, without significantly inhibiting the in vitro growth of PANC-1/Puro cells. All animals inoculated with either PANC-1 or PANC-1/Puro cells, and not given aspirin, developed pancreatic tumors, whereas none of the mice injected with PANC-1/IkappaBalphaM cells showed any evidence of pancreatic tumor formation. Animals given aspirin for 6 days before, or at the time of, orthotopic tumor cell injection showed a significantly lower incidence of tumor formation compared with those receiving aspirin 2 weeks after inoculation and controls receiving no aspirin.

Conclusions: Aspirin repressed tumor formation by PANC-1 cells in vivo in a prophylactic setting, suggesting a possible mechanism for aspirin's preventive effect in pancreatic carcinoma through inhibition of NF-kappaB activation and a mechanistic link between inflammation and tumorigenesis. Aspirin-mediated antiinflammatory approaches might be an effective strategy to prevent pancreatic carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / prevention & control*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / therapeutic use*
  • Cyclooxygenase 2
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / prevention & control*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents, Non-Steroidal
  • Membrane Proteins
  • NF-kappa B
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin