Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines : Growth inhibition by nonsteroidal anti-inflammatory drugs

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 17; pp. 4356 - 4362
• Main Authors: MOLINA, M. A, SITJA-ARNAU, M, LEMOINE, M. G, FRAZIER, M. L, SINICROPE, F. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.1999
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Division - drug effects; Cyclooxygenase 1; Cyclooxygenase 2; Epidermal Growth Factor - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Membrane Proteins; Nitrobenzenes - pharmacology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - enzymology; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; RNA, Messenger - analysis; Sulfonamides - pharmacology; Sulindac - pharmacology; Tumor Cells, Cultured; Tumors; Adenocarcinoma; Human; Prostaglandin-endoperoxide synthase; Enzyme; Gene product; Tumoral tissue; Malignant tumor; Acetic acid derivative; Anticarcinogen; Cell differentiation; Gene expression; In vitro; Non steroidal antiinflammatory agent; In vivo; Messenger RNA; Sulindac; Established cell line; Digestive diseases; Indene derivatives; Oxidoreductases; Pancreas; Tumor cell; Pancreatic disease; Cytostase
• ISSN: 0008-5472; 1538-7445

Cyclooxygenase (COX)-2 mRNA and protein expression were found to be frequently elevated in human pancreatic adenocarcinomas and cell lines derived from such tumors. Immunohistochemistry demonstrated cytoplasmic COX-2 expression in 14 of 21 (67%) pancreatic carcinomas. The level of COX-2 mRNA was found to be elevated in carcinomas, relative to histologically normal pancreas from a healthy individual, as assessed by reverse transcription-PCR. COX-2 protein expression was detected by the Western blot assay in three of five pancreatic carcinoma cell lines (BxPC-3, Capan-1, and MDAPanc-3), whereas COX-1 protein was detected in two of the five cell lines (BxPC-3 and Capan-1). Increased levels of COX-2 mRNA were found in four of five cell lines, and only in PANC-1 cells was the low level of transcript comparable to that in the normal pancreas. The level of COX-2 mRNA was positively correlated with the differentiation status of the tumor of origin for each cell line, COX-2 protein expression was up-regulated by epidermal growth factor when the cells were grown in absence of serum. Finally, two nonsteroidal anti-inflammatory drugs, sulindac sulfide and NS398, produced a dose-dependent inhibition of cell proliferation in all pancreatic cell lines tested. No correlation was found between the level of COX-2 or COX-1 expression and the extent of growth inhibition. Treatment of BxPC-3 cells with sulindac sulfide and NS398 resulted in an induction of COX-2 expression. Our findings indicate that COX-2 up-regulation is a frequent event in pancreatic cancers and suggest that nonsteroidal anti-inflammatory drugs may be useful in the chemoprevention and therapy of pancreatic carcinoma.