Effect of valproate acid sodium on apoptosis of human gastric cancer cells and its mechanism study

OBJECTIVE: To study the effect of valproate acid sodium(VPA) on apoptosis of human gastric cancer cell BGC-823 and to explore its possible mechanism. METHODS: Cell growth inhibition was examined by MTT assay. Apoptosis rate was detected by FCM with Annexin V/PI staining. The activities and protein expression levels of caspase 3, caspase 8 and caspase 9 were examined by spectrophotometry and indirect immunofluorescence technique respectively. RESULTS: The growth inhibition rate and apoptosis rate of human gastric cancer cells, treated with 0.75-4.00 mmol/L VPA for 24 h and 48 h, elevated in time- and dose-dependent manner. Apoptosis rates of VPA 0.75 mmol/L 24 h and 48 h were (7.2 +/- 0.5)% and (9.2 +/- 1.0)%, of VPA 4.00 mmol/L 24 h and 48 h were (16.7 +/- 2.2)% and (20.4 +/- 1.6)% respectively, which were significantly different as compared to the control [24 h, (4.9 +/- 0.2)%, 48 h, (5.1 +/- 0.8)%] (P< 0.001). The activities and protein expression levels of caspase 3 and caspase 9 were up-regulated compared with the control group (P< 0.001), meanwhile the activity and protein expression of caspase 8 enhanced slightly after VPA treatment for 48 h. CONCLUSION: VPA can inhibit the growth and induce the apoptosis of BGC-823 cells mainly through the activation of caspase 9 pathway.