Faculty Collaboration Database

Nuclear factor kappa B activation is a potential target for preventing pancreatic carcinoma by aspirin. Cancer 2005 Jun 15;103(12):2485-90

Date

04/30/2005

Pubmed ID

15861417

DOI

10.1002/cncr.21075

Scopus ID

2-s2.0-20444365468 (requires institutional sign-in at Scopus site)   68 Citations

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-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.

Author List

Sclabas GM, Uwagawa T, Schmidt C, Hess KR, Evans DB, Abbruzzese JL, Chiao PJ

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Cyclooxygenase 2
Female
Gene Expression Regulation, Neoplastic
Humans
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Nude
NF-kappa B
Pancreatic Neoplasms
Prostaglandin-Endoperoxide Synthases
Tumor Cells, Cultured