AKT/GSK-3beta/VEGF signaling is involved in P2RY2 activation-induced the proliferation and metastasis of gastric cancer

Studies have revealed the contribution of ATP-G-protein-coupled P2Y(2) receptor (P2RY(2)) in tumor progression, but the role of P2RY(2) in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY(2) on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY(2) was expressed in GC tissues and GC cell lines. Adenosine triphosphate (ATP) increased the calcium influx in AGS and HGC-27 cells, and was dose-dependent with ATP concentration. ATP and UTP increased the intracellular glycogen content, enhanced the actin fiber stress response, and promoted the proliferation and migration of GC cells, while P2RY(2) competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY(2) expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY(2) increased the expression of Snail, Vimentin, and beta-catenin in GC cells, and down-regulated the expression of E-cadherin, while AR-C118925XX decreased the expression of these genes induced by ATP. Activation of P2RY(2) activated AKT/GSK-3beta/VEGF signal to promote the proliferation of GC cells, and the P13/AKT signaling pathway LY294002 reversed the corresponding phenomenon, but no synergistic pharmacological properties of AR-C118925XX and LY294002 have been found. In vivo experiments showed that ATP-induced tumor growth, while AR-C118925XX inhibited ATP-induced tumor growth. Our conclusion is that P2RY(2) activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY(2) may be a new potential target for the treatment of GC.