Combined valproic acid and celecoxib treatment induced synergistic cytotoxicity and apoptosis in neuroblastoma cells.

BACKGROUND The effects of combined valproic acid (VPA) and celecoxib treatment on cancer cells have not been reported. In this study, we examined the effects of VPA and celecoxib, alone and combined, on human SH-SY5Y neuroblastoma cells. MATERIALS AND METHODS The cytotoxicity effects of VPA, celecoxib, and combined VPA and celecoxib treatment on neuroblastoma cells were studied. The apoptotic fraction and the cell cycle distribution of neuroblastoma cells were analyzed by flow-activated cell sorter analysis. Western blot analysis was used to investigate the expression of cyclooxygenase-2, p53, 14-3-3σ, p21, p27, Bcl-2 and Bax in neuroblastoma cells treated with various regimens. RESULTS Combined VPA and celecoxib treatment caused more cytotoxicity and apoptosis in neuroblastoma cells than individual drug treatment (p<0.05). In addition, combination treatment caused more neuroblastoma cells to accumulate in the G0/G1 phase of the cell cycle (p<0.04) and induced higher p21 and p27 expression than individual drug treatment or control. CONCLUSION Combined VPA and celecoxib treatment induced more cytotoxicity and apoptosis in neuroblastoma cells than individual drug treatment. The effects were probably related to the increased p21 and p27 expression, and G0/G1 accumulation of neuroblastoma cells.