Published online Apr 7, 2007. doi: 10.3748/wjg.v13.i13.1947
Revised: December 3, 2006
Accepted: December 28, 2006
Published online: April 7, 2007
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 (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 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.