脑胶质瘤增殖、迁移和侵袭中的肿胀诱导氯离子电流。

Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion.

机构信息

Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.

Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.

出版信息

J Cell Physiol. 2018 Jan;233(1):363-370. doi: 10.1002/jcp.25891. Epub 2017 Jun 5.

DOI:10.1002/jcp.25891

PMID:28262948

Abstract

Glioblastoma (GBM) remains as the most common and aggressive brain tumor. The survival of GBM has been linked to the aberrant activation of swelling-induced chloride current I . In this study, we investigated the effects of I on cell viability, proliferation, and migration in the human GBM cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. First, we showed that the specific inhibitor of I , DCPIB, potently reduced the I in U87 cells. Next, in both U87 and U251 cells, we found that DCPIB reduced GBM viability, proliferation, colony formation, migration, and invasion. In addition, our Western immunoblot assay showed that DCPIB-treated U251 cells had a reduction in JAK2, STAT3, and Akt phosphorylation, thus, suggesting that DCPIB potentially suppresses GBM functions through inhibition of the JAK2/STAT3 and PI3K/Akt signaling pathways. Therefore, the I may be a potential drug target for GBM.

摘要

胶质母细胞瘤（GBM）仍然是最常见和侵袭性最强的脑肿瘤。GBM 的存活率与肿胀诱导的氯离子电流 I 的异常激活有关。在这项研究中，我们使用膜片钳电生理学、MTT、集落形成、划痕愈合实验和 Western 免疫印迹法，研究了 I 对人 GBM 细胞系 U251 和 U87 中细胞活力、增殖和迁移的影响。首先，我们表明 I 的特异性抑制剂 DCPIB 可有效抑制 U87 细胞中的 I 。接下来，我们发现 DCPIB 在 U87 和 U251 细胞中降低了 GBM 的活力、增殖、集落形成、迁移和侵袭。此外，我们的 Western 免疫印迹分析表明，用 DCPIB 处理的 U251 细胞中 JAK2、STAT3 和 Akt 的磷酸化减少，因此，这表明 DCPIB 通过抑制 JAK2/STAT3 和 PI3K/Akt 信号通路潜在地抑制 GBM 功能。因此，I 可能是 GBM 的一个潜在药物靶点。