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 P2Y2 receptor (P2RY2) in tumor progression, but the role of P2RY2 in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY2 on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY2 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 P2RY2 competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY2 expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY2 increased the expression of Snail, Vimentin, and ß-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 P2RY2 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 P2RY2 activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY2 may be a new potential target for the treatment of GC.

Association between P2X3 receptors and neuropathic pain: As a potential therapeutic target for therapy.

Neuropathic pain is a common clinical symptom of various diseases, and it seriously affects the physical and mental health of patients. Owing to the complex pathological mechanism of neuropathic pain, clinical treatment of pain is challenging. Therefore, there is growing interest among researchers to explore potential therapeutic strategies for neuropathic pain. A large number of studies have shown that development of neuropathic pain is related to nerve conduction and related signaling molecules. P2X3 receptors (P2X3R) are ATP-dependent ion channels that participate in the transmission of neural information and related signaling pathways, sensitize the central nervous system, and play a key role in the development of neuropathic pain. In this paper, we summarized the structure and biological characteristics of the P2X3R gene and discussed the role of P2X3R in the nervous system. Moreover, we outlined the related pathological mechanisms of pain and described the relationship between P2X3R and chronic pain to provide valuable information for development of novel treatment strategies for pain.