Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro

摘要

Background Lumiracoxib is a highly selective cyclooxygenase-2(COX-2)inhibitor with antiinflammatory,analgesic and antipyretic activities comparable with class specific drugs,but with much improved gastrointestinal safety.No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Drug-drug interactions were analyzed using the coefficient of drug interaction(CDI)to characterize the interactions as synergism,additivity or antagonism.Morphological changes were observed by acridine orange fluorescent staining.Extent of apoptosis was determined by flow cytometry.Results Lumiracoxib(15-240 μmol/L)has an inhibitory effect on the proliferation of A549 and NCI-H460 celllines in concentration- and time-dependent manners with the IC50 values of 2597 μmol/L and 833 pmol/L,respectively.The synergistic effect was prominent when lumiracoxib(15-240 μmol/L)was combined with docetaxol(0.2-2 μmol/L)(CDI ＜1).Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells.Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol,which may be related to apoptotic induction and cell cycle arrest.