Journal Article

Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines

Olga N. Tucker, Andrew J. Dannenberg, Eun K. Yang and Thomas J. Fahey

in Carcinogenesis

Volume 25, issue 3, pages 419-423
Published in print March 2004 | ISSN: 0143-3334
Published online March 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh010
Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines

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To investigate a possible link between bile acids and the pathogenesis of pancreatic cancer, we determined whether conjugated or unconjugated bile acids induced cyclooxygenase-2 (COX-2) in two human pancreatic cancer cell lines, BxPC-3 and SU 86.86. Bile acids are known promoters of gastric and colon cancer. We demonstrated previously that COX-2, an enzyme that catalyzes the synthesis of prostaglandins, is over-expressed in human pancreatic adenocarcinoma. Both human pancreatic cell lines were treated with conjugated and unconjugated bile acids. COX-2 mRNA and protein were determined. In addition, prostaglandin E2 (PGE2) synthesis was measured. Treatment with conjugated or unconjugated bile acids for 3 h up-regulated COX-2 mRNA. Chenodeoxycholate (CD) or deoxycholate at concentrations ranging from 12.5 to 100 µM caused a dose-dependent induction of COX-2 protein with a maximal effect at 100 µM. Induction of COX-2 protein by CD and deoxycholate was detected after treatment for 6 h with maximal induction at 12 h. Taurochenodeoxycholate, a conjugated bile acid, also caused dose-dependent induction of COX-2 but higher concentrations of bile acid (200–1200 µM) were required. Levels of cyclooxygenase-1 were unaffected by bile acid treatment. Unconjugated and conjugated bile acids caused 7- and 4-fold increases in PGE2 production, respectively. Taken together, these findings suggest a possible role for bile acids in the pathogenesis of pancreatic cancer.

Keywords: CD, chenodeoxycholic acid; COX-1, cyclooxygenase-1; COX-2, cyclooxygenase-2; cPLA2, cytoplasmic phospholipase A2; DC, deoxycholic acid; FCS, fetal calf serum; GCDC, glycochenodeoxycholic acid; PGE2, prostaglandin E2; TCDC, taurochenodeoxycholic acid

Journal Article.  4376 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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