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溴化阿地溴铵通过 PI3K/AKT 信号通路抑制人神经胶质瘤细胞增殖、迁移和侵袭并促进细胞凋亡。

Aclidinium bromide inhibits human glioma cell proliferation, migration and invasion and promotes apoptosis via the PI3K/AKT signaling pathway.

机构信息

Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Neoplasma. 2018 Nov 15;65(6):865-871. doi: 10.4149/neo_2018_171117N705. Epub 2018 Jun 17.

DOI:10.4149/neo_2018_171117N705
PMID:29940755
Abstract

This study investigates the anti-cancer potential of Aclidinium bromide (INN) in glioblastoma. Glioblastoma cell lines U251 and U87 were treated with INN and its effects on cell migration and invasion were assessed by transwell migration and invasion assays., The effects of INN on proliferation and apoptosis were detected by CCK-8 kit and flow cytometry, and Western blotting determined anti-apoptotic proteins and signaling pathway changes. The results show that INN effectively suppressed proliferation, migration and invasion and induced apoptosis in U251 and U87 cells, respectively. Furthermore, the expression levels of the Bcl-2 anti-apoptotic protein was significantly decreased while Bax and caspase-3 expression were both increased in glioblastoma cells (all, p<0.05). Moreover, INN inactivated the PI3K/AKT signaling pathway by down-regulating the level of p-AKT, p-mTOR, P70 and CyclinD1 (all, p<0.05). In conclusion, our data suggests that INN could provide novel anticancer therapy in the treatment of glioblastoma.

摘要

这项研究旨在探究阿地溴铵(INN)在神经胶质瘤中的抗癌潜力。我们用 INN 处理神经胶质瘤细胞系 U251 和 U87,并通过 Transwell 迁移和侵袭实验评估其对细胞迁移和侵袭的影响。用 CCK-8 试剂盒和流式细胞术检测 INN 对增殖和凋亡的影响,Western blot 检测抗凋亡蛋白和信号通路变化。结果表明,INN 能有效抑制 U251 和 U87 细胞的增殖、迁移和侵袭,并分别诱导其凋亡。此外,神经胶质瘤细胞中 Bcl-2 抗凋亡蛋白的表达水平显著降低,而 Bax 和 caspase-3 的表达均增加(均 p<0.05)。此外,INN 通过下调 p-AKT、p-mTOR、P70 和 CyclinD1 的水平,抑制了 PI3K/AKT 信号通路(均 p<0.05)。综上所述,我们的数据表明,INN 可能为神经胶质瘤的治疗提供新的抗癌疗法。

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