Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines.
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 micro M caused a dose-dependent induction of COX-2 protein with a maximal effect at 100 micro M. 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 micro M) 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.
Tucker
Olga N
ON
Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021, USA. olaga_tucker@hotmail.com
Dannenberg
Andrew J
AJ
Yang
Eun K
EK
Fahey
Thomas J
TJ
D001647:Bile Acids and Salts / Q000378:metabolism*; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008565:Membrane Proteins; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D010741:Phospholipases A / Q000096:biosynthesis / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D015232:Dinoprostone