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

Abstract

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-β1 promoted the migration and invasion of CRC cells, while the application of P2X7R antagonist could inhibit TGF-β1 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 β-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.