title: The role of cyclooxygenase enzymes in the growth of human gall bladder cancer cells.
abstract: Information suggests that the cyclooxygenase (COX) metabolites, the prostanoids, play a role in gall bladder physiology and disease. Non-steroidal anti-inflammatory drugs which inhibit COX enzymes have been shown in vivo and in vitro to alter the growth patterns of intestinal epithelial cells, and specific COX-2 inhibitors have been shown to decrease mitogenesis in intestinal epithelial cells. The present study was intended to evaluate the effect of specific COX inhibitors on the growth patterns of gall bladder cancer cells. Employing a human gall bladder cancer cell line, mitogenesis, apoptosis and prostaglandin E(2) (PGE(2)) formation were evaluated in response to serum and hepatocyte growth factor and transforming growth factor alpha stimulation in the presence and absence of specific COX-1 and -2 inhibitors. The effect of the mitogens on COX enzyme expression was also evaluated. Serum and the growth factors increased COX enzyme expression and mitogenesis, and decreased apoptosis as evaluated by the percentage of cells that were floating in culture media rather than attached. There was more DNA degradation in floating than in attached cells. The specific COX-2 inhibitor, but not the COX-1 inhibitor, decreased mitogenesis and increased gall bladder cell apoptosis as evaluated by the number of floating versus attached cells and the number of floating cells in the terminal phase of apoptosis or dead. The inhibition of mitogenesis and the increased apoptosis produced by the COX-2 inhibitor was associated with decreased PGE(2) production. The inhibition of replication of gall bladder cancer cells and the increase in apoptosis produced by the selective COX-2 inhibitor suggests that the COX enzymes and the prostanoids may play a role in the development of gall bladder cancer and that the COX-2 inhibitors may have a therapeutic role in the prevention of gall bladder neoplasms.
authors.affiliation: Department of Surgery, Saint Louis University School of Medicine, Theodore Cooper Surgical Research Institute, Grand Boulevard at Vista Avenue, PO Box 15250, St Louis, MO 63110-0250, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Grossman
authors.forename: W E
authors.initials: WE
authors.lastname: Longo
authors.forename: N
authors.initials: N
authors.lastname: Panesar
authors.forename: J E
authors.initials: JE
authors.lastname: Mazuski
authors.forename: D L
authors.initials: DL
authors.lastname: Kaminski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins; D008934:Mitogens / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004273:DNA, Neoplasm; D007527:Isoenzymes; D008565:Membrane Proteins; D008934:Mitogens; D011720:Pyrazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone