Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak

Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and casp ases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53 ) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expre ssions were determined by western blotting. Aspirin and indomethacin inhibi ted cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax a nd bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibit ion of caspase-3 rescued aspirin-induced apoptosis. Our results suggest tha t one of the major pathways which mediates the anti-tumour response of aspi rin and indomethacin in gastric cancer cells is through up-regulation of ba x and bak and activation of caspase-3. Bax and bak are important in the che moprevention of gastric cancer.