Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment
Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment
复制标题
在替莫唑胺诱导的胶质瘤细胞生长抑制和侵袭损伤中通过 p38 MAPK 信号下调 AQP4 表达
DOI：
10.1002/jcb.26176
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Yang, Mei
中科院分区：
文献类型：
--
作者：
Chen, Yuqin;Gao, Fei;Yang, Mei
神经胶质瘤是最常见和致命的中枢神经系统肿瘤。替莫唑胺（TMZ）是一种有效的恶性神经胶质瘤药物，但是，这种抗癌作用背后的细胞内和分子机制尚未完全了解。本研究的目的是确定TMZ是否抑制了在体外的增殖，侵袭神经胶质瘤细胞的侵袭以及是否可以通过调节水通道蛋白4（AQP4）（AQP4）和MAPK途径的磷酸化来介导这些作用。使用MTT测定法评估了U87和U251人神经胶质瘤细胞的生存能力。通过流式细胞仪检测细胞周期分布。分别通过刮擦分析和transwell测定法测试迁移能力和入侵能力。使用免疫印迹分析测量了AQP4和MAPK的水平。我们的结果表明，TMZ抑制了U87和U251神经胶质瘤细胞系中的G2/M停滞，抑制了增殖，迁移和侵袭。这些变化与AQP4表达水平的降低以及p38的磷酸化水平有关。用p38化学激活剂（砷霉素）处理与TMZ治疗对神经胶质瘤细胞的影响相似。 P38化学抑制剂（SB203580）可以阻止用TMZ处理的神经胶质瘤的这些作用，这表明p38信号通路的直接上调。因此，我们确定TMZ可能具有通过激活p38信号转导途径抑制AQP4表达来控制增殖，侵袭恶性神经胶质瘤的治疗潜力。 J. Cell。生物化学。 118：4905-4913，2017。
Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. (c) 2017 Wiley Periodicals, Inc.