title: Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells.
abstract: Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p<0.01). A more pronounced decrease (23-27%, p<0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p<0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p<0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.vanheumen@mdl.umcn.nl
authors.forename: Bjorn W H
authors.initials: BW
authors.lastname: van Heumen
authors.forename: Hennie M J
authors.initials: HM
authors.lastname: Roelofs
authors.forename: René H M
authors.initials: RH
authors.lastname: Te Morsche
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
authors.forename: Fokko M
authors.initials: FM
authors.lastname: Nagengast
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
mesh_terms: D000236:Adenoma / Q000188:drug therapy*; D011125:Adenomatous Polyposis Coli / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D002756:Cholagogues and Choleretics; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D000068579:Celecoxib