Targeted Antagonistic ATP-Gated P2X7 Receptor Inhibits the Migration and Invasion of Hepatocellular Carcinoma Cells.

INTRODUCTION: Although some molecular genes in the pathological mechanism of hepatocellular carcinoma (HCC) have been explored, determining the molecular targets and functional roles in the progress of HCC has important clinical significance for the prevention and treatment of HCC. The ATP-gated P2X7 receptor (P2RX7) is an ion channel-type receptor that is expressed in most tumors and regulates tumor progression. However, the relationship between P2RX7 expression and HCC patients and its functional role in HCC migration and invasion need to be further investigated and determined.

MATERIALS AND METHODS: In this study, we investigated the correlation between P2RX7 expression in HCC patients. The effect of P2RX7 on the migration and invasion of HCC cells was further investigated through functional experiments.

RESULTS: The results showed that P2RX7 showed a high expression pattern in HCC patients, and its high expression was negatively correlated with the prognosis of HCC patients. BzATP (an ATP-like agonist) activates the P2RX7 to open calcium channels in HCC cells and promote calcium influx, while P2RX7 antagonists AZD9056 and A438079 significantly prevent calcium influx. Interestingly, P2RX7 activation promotes HCC cell migration, invasion, and glycogen metabolism, while the use of its antagonist reverses related phenomena. Moreover, P2RX7 in HCC tissue is closely related to the PKC pathway. BzATP increases the level of PKC phosphorylation, while antagonistic P2RX7 decreases the level of PKC phosphorylation.

CONCLUSIONS: Our conclusion shows that targeted antagonism of P2RX7 activity inhibits the migration and invasion of HCC cells, and its functional mechanism may be mediated by the PKC signaling pathway. These data suggest the intrinsic correlation between P2RX7 and HCC and reveal that targeting P2RX7 may become another molecular basis for preventing and treating HCC.