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Celecoxib attenuates 5-fluorouracil-induced apoptosis in HCT-15 and HT-29 human colon cancer cells

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Authors
Lim, Yun Jeong; Rhee, Jong Chul; Bae, Young Mee; Chun, Wan Joo
Issue Date
2007-04-28
Publisher
WJG Press
Citation
World J Gastroenterol 2007; 13: 1947-1952
Keywords
Adenocarcinoma/*drug therapy/pathologyAntimetabolites, Antineoplastic/pharmacokinetics/*pharmacology/therapeuticuseAntineoplastic Combined Chemotherapy Protocols/therapeutic useApoptosis/*drug effectsCell Cycle/drug effectsCell Line, TumorColonic Neoplasms/*drug therapy/pathologyCyclooxygenase Inhibitors/*pharmacology/therapeutic useDose-Response Relationship, DrugDrug InteractionsFluorouracil/pharmacokinetics/*pharmacology/therapeutic useHT29 CellsHumansPyrazoles/*pharmacology/therapeutic useSulfonamides/*pharmacology/therapeutic use
Abstract
AIM: To investigate the combined chemotherapeutic effects of celecoxib when used with 5-FU in vitro. METHODS: Two human colon cancer cell lines (HCT-15 and HT-29) were treated with 5-FU and celecoxib, alone and in combination. The effects of each drug were evaluated using the MTT [3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, flow cytometry, and western blotting. RESULTS: 5-FU and celecoxib showed a dose-dependent cytotoxic effect. When treated with 10(-3) mol/L 5-FU (IC(50)) and celecoxib with its concentration ranging from 10(-8) mol/L to 10(-4) mol/L of celecoxib, cells showed reduced cytotoxic effect than 5-FU (10(-3) mol/L) alone. Flow cytometry showed that celecoxib attenuated 5-FU induced accumulation of cells at subG1 phase. Western blot analyses for caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage showed that celecoxib attenuated 5-FU induced apoptosis. Western blot analyses for cell cycle molecules showed that G2/M arrest might be possible cause of 5-FU induced apoptosis and celecoxib attenuated 5-FU induced apoptosis via blocking of cell cycle progression to the G2/M phase, causing an accumulation of cells at the G1/S phase. CONCLUSION: We found that celecoxib attenuated cytotoxic effect of 5-FU. Celecoxib might act via inhibition of cell cycle progression, thus preventing apoptosis induced by 5-FU.
ISSN
1007-9327 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17461495

http://hdl.handle.net/10371/28634
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College of Medicine/School of Medicine (의과대학/대학원)Parasitology and Tropical Medicine (기생충학전공)Journal Papers (저널논문_기생충학전공)
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