The Effects And Mechanism Of COX-2 Inhibitor Celecoxib In Inhibiting MCF-7 Cells Proliferation And Enhancing Chemotherapy Efficacy

Objective: To investigate whether the selective COX-2 inhibitorcelecoxib can inhibit breast cancer cells MCF-7 proliferation, whichexpress a low level of COX-2; to investigate whether celecoxib canincrease chemotherapy effect of epirubicin on MCF-7 cells and itsmechanism.Methods: To confirm whether MCF-7cells express a low level ofCOX-2 by RT-PCR. MCF-7 cells were interfered with differentconcertrations of celecoxib, then the effects were observed by MTT assay.MCF-7 cells were treated with epirubicin, low dose Celecoxib andCelecoxib together with epirubicin, then the effects and probablemolecular mechanism of the drugs on MCF-7 cells proliferation andapoptosis were analyzed by MTT assay, flow cytometry, westernblotting.Results:1. MCF-7 cells expressed COX-2 in a low level, compared with lungcancer cells A549 which expressed COX-2 in a high level.2. Celecoxib inhibited MCF-7 cells growth in a dose- andtime-dependent manner.3. 10μmol/L celecoxib combined with 10μg/ml epirubicin inhibitedMCF-7 cells proliferation and induced MCF-7 cells apoptosis more prominently than they did respectively.4. "Celecoxib+epirubicin" could cause up-regulation and cleavageof caspase-3 and down-regulation of bcl-2, but the change of bax wasnot significant.Conclusion:1. Celecoxib inhibited MCF-7 cells growth in a dose- and timedependent manner, which was not obvious correlation with COX-2.2. Celecoxib can enhance the anti-MCF-7 cells effects of epirubicin,and the molecular mechanism may relate to up-regulation of caspase-3and down-regulation of bcl-2.