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

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-dimethylth...

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Bibliographic Details
Published in:World journal of gastroenterology : WJG 2007-04, Vol.13 (13), p.1947-1952
Main Authors: Lim, Yun-Jeong, Rhee, Jong-Chul, Bae, Young-Mee, Chun, Wan-Joo
Format: Article
Language:English
Subjects:
5-FU
Adenocarcinoma - drug therapy
Adenocarcinoma - pathology
Antimetabolites, Antineoplastic - pharmacokinetics
Antimetabolites, Antineoplastic - pharmacology
Antimetabolites, Antineoplastic - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Apoptosis - drug effects
Basic Research
Celecoxib
Cell Cycle - drug effects
Cell Line, Tumor
Colonic Neoplasms - drug therapy
Colonic Neoplasms - pathology
Cyclooxygenase Inhibitors - pharmacology
Cyclooxygenase Inhibitors - therapeutic use
Dose-Response Relationship, Drug
Drug Interactions
Fluorouracil - pharmacokinetics
Fluorouracil - pharmacology
Fluorouracil - therapeutic use
HCT-15
HT-29
HT29 Cells
Humans
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Sulfonamides - pharmacology
Sulfonamides - therapeutic use
塞来考昔
细胞凋亡
结肠癌细胞
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Summary: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 dosedependent cytotoxic effect. When treated with 10-3 mol/L 5-FU （IC50） 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 GI/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
2219-2840
DOI:10.3748/wjg.v13.i13.1947