Involvement of P2X7 Receptor in Proliferation and Migration of Human Glioma Cells.

Yuting Xie,Yu Guan,Yujian Zhang,Kin-Sang Cho,Yongping You,Zhenhua Ji,Min Ji

doi:10.1155/2018/8591397

Abstract

Previous studies have demonstrated that activation of P2X7 receptors (P2X7R) results in the proliferation and migration of some types of tumor. Here, we asked whether and how the activated P2X7R contribute to proliferation and migration of human glioma cells. Results showed that the number of P2X7R positive cells was increasing with grade of tumor. In U87 and U251 human glioma cell lines, both expressed P2X7R and the expression was enhanced by 3′-O-(4-benzoylbenzoyl) ATP (BzATP), the agonist of P2X7R, and siRNA. Our results also showed that 10 μM BzATP was sufficient to induce the proliferation of glioma cell significantly, while the cell proliferation reached the peak with 100 μM BzATP. Also, the migration of U87 and U251 cells was significantly increased upon BzATP treatment. However, the number of apoptotic cells of U87 and U251 was not significantly changed by BzATP. In addition, the expression of ERK, p-ERK, and proliferating cell nuclear antigen (PCNA) protein was increased in BzATP-treated U87 and U251 glioma cells. PD98059, an inhibitor of the MEK/ERK pathway, blocked the increased proliferation and migration of glioma cells activated by BzATP. These results suggest that ERK pathway is involved in the proliferation and migration of glioma cells induced by P2X7R activation.

Highlights

Malignant glioma is the most common malignant tumor of the central nervous system [1]
We found that P2X7 receptors (P2X7R) positive glial cells were rarely seen in normal tissues
We found that the proliferation of U87 and U251 glioma cell lines was significantly increased in the presence of 10–1000 uM and 100–1000 μM BzATP, respectively

Summary

Introduction

Malignant glioma is the most common malignant tumor of the central nervous system [1]. Brief exposure to P2X7R agonist such as ATP or 3󸀠-O-(4benzoylbenzoyl) ATP (BzATP) leads to the opening of cation channel allowing K+ efflux and Ca2+ and Na+ influx into the cells [12]. Previous studies have shown that activation of P2X7R can induce angiogenesis, increase vascular endothelial growth factor production, accelerate cell invasion and migration, and promote tumor growth [16, 17]. Other studies showed that inhibiting the activation of P2X7R induced tumor growth and accelerated tumor cell death [19, 20]. P2X7R in glioma cell proliferation and migration remains unclear. We examined the role of P2X7R on the migration, cell proliferation, and downstream signaling pathways using human glioma cell lines and human glioma tissues

Materials and Methods

Results

Discussion