Apoptosis induction in gastric carcinoma cells by celecoxib combined with adriamycin

AIM:To study the apoptosis induction of cyclooxygenase-2 (COX-2) inhibitor，celecoxib and adriamycin (ADM) on tumor apoptosis of gastric carcinoma MGC-803 cells, and to explore their possible molecular mechanism(s) and interactions.METHODS:The number of MGC-803 cells was observed by MTT assay. Tumor apoptosis was studied by fluorescence microscopy, flow cytometry (FCM), and DNA ladder. RESULTS:MGC-803 cell number was significantly decreased with increasing dose of ADM. Cells were accumulated in G₀/G₁ phase and the number of cells in S phase was decreased. ADM (5 mg/L) combined with celecoxib (25 μmol/L) markably inhibited the growth of MGC-803 cells. Significant morphological changes of typical apoptosis were observed after treatment with combined use of celecoxib and ADM. Compared with ADM or celecoxib alone, ADM plus celecoxib obviously enhanced the DNA ladder fragment revealed by agarose gel electrophoresis of DNA. After exposure to combined celecoxib and ADM treatment for 48 h, MGC-803 cells were accumulated in G₀/G₁ phase. There was a decrease in the number of cells in S phase as compared to celecoxib or ADM alone. CONCLUSION:Celecoxib and ADM appear to have synergistic effects for the apoptosis induction. This may be an important prospect for applying COX-2 inhibitors to assist chemical therapy of ADM in clinical use.