Abstract:  Abstract　Objective: To investigate the mechanism of celecoxib regulation on the apoptosis of human gastric cancer cell via the PI3K/Akt signaling pathway. Methods: After in vitro celecoxib treatment of the SGC-7901cell line, transmission electron microscopy (TEM) was used to observe the morphologic changes in cellular ultrastructure. Real-time quantitative polymerase chain reaction and Western blot analysis were used to analyze the changes in the mRNA and the protein levels of Akt, caspase-8, and caspase-9 in SGC-7901 cells after celecoxib treatment. Results: Apoptotic changes, such as nuclear envelope subsidence, chromatin margination, crescent formation of the nucleus, apoptotic bodies, and autophagosomes, were observed under TEM. Interestingly, intense autophagic vacuolization and autophagosomes were detected in the regional cytoplasm of the affected cells. There was no statistically significant change in Akt mRNA and p-Akt protein expression in the experiment group. There was a decrease in p-Akt protein expression in a time-dose dependent manner. The changes were statistically significant ( P < 0.05 or P < 0.01 ). Caspase-8 mRNA expression increased sharply in a time-dose dependent manner and the change was statistically significant ( P < 0.05 or P < 0.01 ). Caspase-9 mRNA expression increased in the experimental group compared with the control; however, no statistically significant difference between the changes in caspase-9 mRNA levels in the group treated with 125 μmol/L celecoxib for 24 h and those in the control group. Significant differences were observed between the caspase-9 mRNA expression in the group treated with 125 μmol/L celecoxib for 48 and 72 h and those in the control group ( P < 0.05 and P < 0.01 ). At 72 h after celecoxib treatment, no statistically significant difference in caspase-9 mRNA expression was observed between the group treated with 75 μmol/L and the control group. Significant differences were found between the caspase-9 mRNA expression in the groups treated with 100 μmol/L and with 125 μmol/L and those in the control ( P < 0.05 and P < 0.01 ). The procaspase-8 and procaspase-9 proteins were activated, and the protein expression decreased. The expression was affected in a time-dose dependent manner, with significant differences among the groups ( P < 0.05 or P < 0.01 ). Conclusion: 1) Celecoxib may result in cell death via two mechanisms, namely, apoptosis and autophagic cell death induced through the PI3K/Akt signaling pathway. 2) The mechanisms by which celecoxib induces apoptosis are the death-receptor pathway and the mitochondrial pathways.