P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research)
Wenjun Zhang, Hongliang Luo, Jipeng Liu, Yongsheng Xu, Wenlong Wang, Chao Huang
Abstract
OBJECTIVE: This study investigated the role of P2X7 receptor (P2X7R) in the proliferation and metastasis of gastric cancer (GC). METHODS: The functional role and possible mechanism of P2X7R in the progression of GC were investigated through in vitro and in vivo experiments. RESULTS: The results showed that ATP and its analogue BzATP increased calcium current in AGS and HGC-27 cells, while P2X7R antagonists A438079 and AZD9056 decreased the ATP-induced calcium influx. Activation of P2X7R increased the glycogen accumulation in GC cells, enhanced the stress ability of actin fibers and cell morphology changes, and promoted the proliferation, migration and invasion of GC cells. Conversely, the application of A438079, AZD9056 or siP2X7R inhibited the proliferation, migration and invasion of GC cells. Moreover, activation of P2X7R increased the expression levels of EMT/metastasis related genes MMP-2, MMP-9, N-cadherin, Zeb1, Vimentin and Snail, hut decreased the E-cadherin expression. While A438069, AZD9056, LY294002 or siP2X7R reversed the expression of the above genes. Activation of P2X7R activated P13/AKT/GSK-3beta signaling to promote the proliferation, migration and invasion of GC. Additionally, in vivo experiments showed that ATP activated P2X7R to induce the growth of tumors. CONCLUSIONS: Our conclusion is that activation of P2X7R promotes the proliferation, metastasis and EMT of GC cells by activating P13/AKT/GSK-3beta signaling, and indicates that P2X7R may become a new potential target for GC treatment.