Department of Neurosurgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Department of Head and Neck Surgery, Affiliated Tumor Hospital of Nantong University, Nantong 226001, China.
Biomed Res Int. 2018 Jan 9;2018:8591397. doi: 10.1155/2018/8591397. eCollection 2018.
Previous studies have demonstrated that activation of P2X receptors (P2XR) results in the proliferation and migration of some types of tumor. Here, we asked whether and how the activated P2XR contribute to proliferation and migration of human glioma cells. Results showed that the number of P2XR positive cells was increasing with grade of tumor. In U87 and U251 human glioma cell lines, both expressed P2XR and the expression was enhanced by 3'-O-(4-benzoylbenzoyl) ATP (BzATP), the agonist of P2XR, and siRNA. Our results also showed that 10 M BzATP was sufficient to induce the proliferation of glioma cell significantly, while the cell proliferation reached the peak with 100 M 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 P2XR activation.
先前的研究表明，P2X 受体 (P2XR) 的激活会导致某些类型的肿瘤增殖和迁移。在这里，我们想知道激活的 P2XR 是否以及如何促进人神经胶质瘤细胞的增殖和迁移。结果表明，P2XR 阳性细胞的数量随着肿瘤分级的增加而增加。在 U87 和 U251 人神经胶质瘤细胞系中，均表达 P2XR，并且 P2XR 的激动剂 3'-O-(4-苯甲酰基苯甲酰基)ATP (BzATP) 和 siRNA 增强了其表达。我们的结果还表明，10μM BzATP 足以显著诱导神经胶质瘤细胞增殖，而 100μM BzATP 使细胞增殖达到峰值。此外，BzATP 处理可显著增加 U87 和 U251 细胞的迁移。然而，BzATP 并未使 U87 和 U251 细胞的凋亡细胞数量发生明显变化。此外，BzATP 处理的 U87 和 U251 神经胶质瘤细胞中 ERK、p-ERK 和增殖细胞核抗原 (PCNA) 蛋白的表达增加。MEK/ERK 通路的抑制剂 PD98059 阻断了 BzATP 激活的神经胶质瘤细胞增殖和迁移的增加。这些结果表明，ERK 通路参与了 P2XR 激活诱导的神经胶质瘤细胞的增殖和迁移。
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