Abstract
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-κB) 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/IκBαM was used to study the inhibitory effects of aspirin on pancreatic tumor formation. RESULTS. Aspirin inhibited constitutive NF-κB activity in culture and, in turn, decreased the expression of the NF-κB 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/IκBαM 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-κB activation and a mechanistic link between inflammation and tumorigenesis. Aspirin-mediated antiinflammatory approaches might be an effective strategy to prevent pancreatic carcinoma.
Original language | English (US) |
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Pages (from-to) | 2485-2490 |
Number of pages | 6 |
Journal | Cancer |
Volume | 103 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2005 |
Keywords
- Aspirin
- Chemoprevention
- Genetic alterations
- Inflammation
- Nuclear factor kappa B
- Pancreatic carcinoma
- Tumorigenesis
ASJC Scopus subject areas
- Oncology
- Cancer Research