Involvement of P2X(7) Receptor in Proliferation and Migration of Human Glioma Cells.

Involvement of P2X(7) Receptor in Proliferation and Migration of Human Glioma Cells.
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P2X7受体参与人胶质瘤细胞的增殖和迁移

DOI:
10.1155/2018/8591397
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发表时间:
2018
影响因子:
--
通讯作者:
You Y
You Y
中科院分区:
生物学3区
文献类型:
--
作者:
Ji Z;Xie Y;Guan Y;Zhang Y;Cho KS;Ji M;You Y

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以往的研究表明,P2 X7受体(P2 X7 R)的激活导致某些类型的肿瘤的增殖和迁移。在这里,我们问激活的P2 X7 R是否以及如何有助于人类胶质瘤细胞的增殖和迁移。结果显示,P2 X7 R阳性细胞数随肿瘤分级的增高而增多。在U87和U251胶质瘤细胞系中均表达P2 X7 R,P2 X7 R激动剂3′-O-(4-benzoylbenzoyl)ATP(BzATP)和siRNA可增强P2 X7 R的表达。10 μM BzATP对胶质瘤细胞有明显的促增殖作用,而100 μM BzATP对胶质瘤细胞的促增殖作用最强。此外,U87和U251细胞的迁移在BzATP处理后显著增加。BzATP对U87和U251细胞凋亡无明显影响。此外,ERK,p-ERK和增殖细胞核抗原(PCNA)蛋白的表达增加BzATP处理的U87和U251胶质瘤细胞。MEK/ERK通路抑制剂PD 98059可阻断BzATP激活的胶质瘤细胞的增殖和迁移。这些结果提示ERK通路参与了P2 X7 R激活诱导的胶质瘤细胞增殖和迁移。
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.
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