The role and pharmacological characteristics of ATP-gated ionotropic receptor P2X in cancer pain.

Many factors are involved in the development of cancer pain, which is a serious complication of cancer and affects the quality of life of patients, Normally, drugs are used to relieve pain in clinic, but the effect is not satisfactory to patients. Therefore, it is necessary to explore the molecular basis of the pathogenesis of cancer pain and carry out targeted therapy. Fortunately, the important role of P2X purine receptors dependent on ATP ion channels in the development of cancer pain has been recognized. In the development of cancer, ATP concentration in the tumor microenvironment is high enough to activate P2X purine receptors, sensitive peripheral receptors, enhance sensory nerve fiber information transmission, sensitize the central nervous system, and induce or aggravate pain. Here, we outlined the role of P2X purine receptors in the development of cancer, and discussed the intrinsic correlation between P2X purine receptors and cancer pain. Moreover, we also explored the pharmacological properties of P2X antagonists or inhibitors to inhibit cancer pain, and hope to provide some value for the treatment of cancer pain in the future. In short, up-regulation of P2X expression can induce or aggravate cancer pain, while reducing P2X expression level can inhibit cancer pain. Therefore, P2X may be another potential pharmacological target for the treatment of cancer pain.

Role and therapeutic target of P2X2/3 receptors in visceral pain.

Visceral pain (VP) is caused by internal organ disease. VP is involved in nerve conduction and related signaling molecules, but its specific pathogenesis has not yet been fully elucidated. Currently, there are no effective methods for treating VP. The role of P2X2/3 in VP has progressed. After visceral organs are subjected to noxious stimulation, cells release ATP, activate P2X2/3, enhance the sensitivity of peripheral receptors and the plasticity of neurons, enhance sensory information transmission, sensitize the central nervous system, and play an important role in the development of VP. However, antagonists possess the pharmacological effect of relieving pain. Therefore, in this review, we summarize the biological functions of P2X2/3 and discuss the intrinsic link between P2X2/3 and VP. Moreover, we focus on the pharmacological effects of P2X2/3 antagonists on VP therapy and provide a theoretical basis for its targeted therapy.

PI3K/Akt/GSK-3ß signal pathway is involved in P2X7 receptor-induced proliferation and EMT of colorectal cancer cells.

P2X7 receptor (P2X7R) plays an important role in regulating the growth of tumor cells. However, the role of P2X7R in colorectal cancer (CRC) has remained poorly understood. Therefore, in this study, in vivo and in vitro experiments were performed to investigate the effect of P2X7R on the proliferation of CRC. The results showed that P2X7R was expressed in CRC cell lines (SW620 and HCT116). ATP and BzATP increased the expression of P2X7R in CRC cells, while the application of P2X7R antagonist A438079 and AZD9056 decreased the P2X7R expression induced by BzATP. Moreover, ATP and BzATP induced the activation of P2X7R to promote the proliferation, migration and invasion of CRC cells. Conversely, A438079, AZD9056 or siRNA transfection targeting P2X7R (siP2X7R) knockdown P2X7R expression inhibited the proliferation and migration of CRC cells. TGF-ß1 promoted the migration and invasion of CRC cells, while the application of P2X7R antagonist could inhibit TGF-ß1 induced migration of CRC cells. Furthermore, activation of P2X7R increased the expression of Vimentin, Snail, Fibronectin and decreased the expression of E-cadherin. While reducing the expression of P2X7R could inhibit these genes expression. In addition, ATP and BzATP increased the expression of p-Akt, p-GSK-3beta and ß-catenin via P2X7R. P13/Akt pathway inhibitor LY294002 inhibited the proliferation of CRC cells, and the P13/Akt signaling was required for BzATP induced the proliferation of CRC cells. Our conclusion is that P2X7R mediated the PI3K/Akt/GSK-3beta signaling to promote the proliferation and EMT of CRC, indicating that P2X7R may be used as a potential therapeutic target for CRC.