[Celecoxib promotes apoptosis of breast cancer cell line MDA-MB-231 through down-regulation of the NF-kappaB pathway].

BACKGROUND AND OBJECTIVE

Celecoxib can inhibit cell proliferation, regulate cell cycle and induce apoptosis, but the underlying mechanisms are still unclear. This study was to investigate the association between the NF-kappaB (kappaB) pathway and the apoptosis of breast cancer cell line MDA-MB-231 induced by celecoxib.

METHODS

The expression of cyclo-oxygenase-2 (COX-2) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation and cell cycle were detected by MTT and flow cytometry (FCM), respectively. The protein expressions of caspase-3 and p65 in MDA-MB-231 cells were detected by western blot.

RESULTS

After incubation with different concentrations of celecoxib for 48 h, COX-2 mRNA expression in MDA-MB-231 cells was decreased in a dose-dependent manner compared with untreated cells (P<0.05). Proliferation of MDA-MB-231 cells was reduced drastically in a dose-and time-dependent manner after celecoxib treatment (P<0.05). Combination of prostaglandin E2 (PGE2) and celecoxib exerted similar inhibition effect to celecoxib alone on cell growth (P>0.05). High-dose celecoxib induced an increase in the percentage of G0/G1 phase cells accompanied by the change in DNA ploidy. The cellular caspase-3 level was enhanced whereas the p65 level was decreased in celecoxib-treated MDA-MB-231 cells after 24 h in comparison to those in the control cells.

CONCLUSION

Celecoxib could inhibit MDA-MB-231 cell proliferation and promote cell apoptosis by down-regulating the NF-kappaB signaling pathway.