BACKGROUNDIn recent years, many investigations have showed that COX-2 inhibitors not only inhibit the growth of tumor cells but also enhance the cytotoxicity of anticancer drugs, such as NS-398, a selective COX-2 inhibitor. But the effect of NS-398 combined with chemotherapy agent cisplatin on growth of lung adenocarcinoma cells and its mechanism are still unknown. The aim of this study is to investigate the effect of NS-398 combined with cisplatin on proliferation of human lung adenocarcinoma cell lines, and to explore their mechanisms.

METHODSSynergistic effect of NS-398 and cisplatin on proliferation of human lung adenocarcinoma cell lines was detected by MTT growth assay, and data were analyzed by SPSS general linear models procedure to determine the IC₅₀ of each drug alone. Combined index (CI) was analyzed to determine the combined effect of drugs. Apoptosis and cell cycle distribution were detected by fluorescence staining of Acridine orange (AO) and Ethidium bromide (EB) and flow cytometry.

RESULTSThe various concentration of NS-398 in combination with cisplatin resulted in the reduction of IC₅₀ of cisplatin by 48.25%-62.44% in A549 cells, and by 43.34%-69.61% in SPC-A-1 cells. The CI of NS-398 and cisplatin in the two cell lines ranged from 0.4 to 0.9, which indicated that they acted in slight synergistic to synergistic pattern. The apoptotic rate at 24h and 48h in the combined groups was significantly higher than those of the control groups, and the S-phase cell fractions at 48h and 72h were obviously higher than those of the control groups. There was a positive correlation between apoptotic rate and S-phase cell fraction in the combined groups (r=0.882,P= 0.01).

CONCLUSIONSNS-398 can improve growth inhibition of cisplatin on lung adenocarcinoma cells, and the two agents act in synergistic way. This synergistic effect may be related to apoptosis pathway.