AZD-9056

The purpose of this study was to investigate the effect of the purinergic ion channel-type P2X7 receptor (P2X7R) on the progression of gastric cancer (GC). Therefore, in this study, in vivo and in vitro experiments were performed to investigate the molecular mechanism of P2X7R on the progression of GC. The results showed that adenosine triphosphate (ATP) and benzoyl ATP (BzATP) activate P2X7R and increased the intracellular calcium concentration of 7901 and 803 cells, and enhanced the migration abilities of GC cells. While P2X7R antagonists (A438079 and AZD9056) decreased the ATP-induced calcium influx, and inhibited the migration abilities of GC cells. This may be related to the stress of actin fibers, which causes the change in cell morphology. Moreover, activation of P2X7R increased the expression of small-conductance Ca^2 + -activated K⁺ channel (SK3) and promoted the migration of GC cells. While A438079 or siRNA transfected cells to knock down the expression of P2X7R and reduced the expression of SK3. The use of SK3 channel inhibitor Apamin inhibited ATP-induced calcium influx and the migration of GC cells. It is interesting that Apamin and A438079 or AZD9056 have a synergistic inhibitory effect. Furthermore, in vivo experiments showed that ATP induced tumor growth, while AZD9056 inhibited ATP-induced tumor growth. Our conclusion is that P2X7R activation promotes the migration and growth of GC cells by opening SK3 channel, and also indicates that P2X7R may become a new potential target for GC treatment.