Activation of P2X7 Receptor Promotes the Proliferation of Colorectal Cancer by Mediating mTOR Signaling

Different studies have shown that P2X7 receptor (P2X7R) is expressed in most tumors and plays an important role in regulating the growth, proliferation, apoptosis, migration and invasion of tumor cells. However, the role of P2X7R in colorectal cancer (CRC) has remained poorly understood. Therefore, the main purpose of this study is to investigate the effect of P2X7R on CRC and related molecular mechanisms, and add new understanding to the molecular basis of CRC. We found that P2X7R was highly expressed in patients with CRC tissues and was closely related to clinicopathological features. Moreover, P2X7R was expressed in CRC cell lines (SW480, HT-29, LoVo, HCT116, and SW620), especially in SW480 and LoVo cells. Functional experiments showed that ATP or BzATP induced P2X7R activation promoted the proliferation, migration and invasion of CRC cells. Conversely, P2X7R antagonist (A438079 or AZD9056) or siRNA transfection targeting P2X7R (siP2X7R) knockdown P2X7R expression inhibited the proliferation of CRC cells. Furthermore, P2X7R activation promoted cyclin-D1 in CRC cells, activated the mTOR signaling pathway, regulated the expression of GP73, 4EBO1, Bcl-2, E-cadherin, Vimentin, MMP-9, VEGF, Bax, and Bcl-2, and promoted proliferation of CRC cells, revealing the mechanism of P2X7R promotes the development of CRC. Our conclusion is that the current findings of this study provide convincing evidence that P2X7R plays an important role in promoting the proliferation of CRC via mTOR signaling, which provides a new theoretical basis for the molecular mechanism of CRC progression, indicating that P2X7R can be used as a potential pharmacological target for the treatment of patients with CRC.<br><br>Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (81760418 and 81260190), the Natural Science Foundation of Jiangxi Province (20181BBG70015 and 20181BAB205061).<br><br>Declaration of Interests: The authors declare that they have no competing interests.<br><br>Ethics Approval Statement: Ethical approval has been exempted by our institution's ethics committee (The Ethics Committee of Nanchang University). All protocols were approved by the Animal Care and Ethics Committee, China.