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-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.