Nuclear factor kappa B activation is a potential target for preventing pancreatic carcinoma by aspirin
✍ Scribed by Guido M. Sclabas; Tadashi Uwagawa; Christian Schmidt; Kenneth R. Hess; Douglas B. Evans; James L. Abbruzzese; Paul J. Chiao
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 615 KB
- Volume
- 103
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
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. Cancer 2005. © 2005 American Cancer Society.