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白花丹醌通过下调MMP - 2/9表达及抑制PI3K/Akt信号通路的活性在体外抑制胶质瘤细胞的迁移和侵袭。

Plumbagin suppresses the migration and invasion of glioma cells via downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway in vitro.

作者信息

Chen Guanghui, Yue Yan, Qin Jun, Xiao Xinping, Ren Qing, Xiao Bin

机构信息

Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.

Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.

出版信息

J Pharmacol Sci. 2017 May;134(1):59-67. doi: 10.1016/j.jphs.2017.04.003. Epub 2017 Apr 24.

Abstract

Plumbagin is a natural naphthoquinone constituent isolated from the roots of medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative and anti-invasion activities in various cancer cells. However, its effect on the migration and invasion of glioma cells has not been elucidated. Therefore, human glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 μM for 24 h, and cell migration and invasion were assessed with scratch wound healing and invasion assays. The results showed that plumbagin significantly inhibited the migration and invasion of U87 and U251 cells, suppressed the activity and expression of MMP-2/-9, and inhibited the nuclear translocation of transcription factors Sp1 in the U87 and U251 cells. Moreover, plumbagin reduced the level of p-PI3K and p-Akt in these cells. The combined treatment with plumbagin and PI3K/Akt agonist insulin-like growth factor-1 (IGF-1) reversed plumbagin-mediated inhibitory effects on MMP-2/-9 expression, cell migration and invasion. These findings suggest that the plumbagin-induced inhibition of glioma cell migration and invasion is closely associated with the downregulation of MMP-2/-9 expression and activity, and suppression of PI3K/Akt signaling pathway activation. Thus, plumbagin might be a potential anti-invasive agent in the treatment of glioma.

摘要

白花丹醌是从药用植物白花丹的根部分离出的一种天然萘醌成分,已在多种癌细胞中显示出抗增殖和抗侵袭活性。然而,其对胶质瘤细胞迁移和侵袭的影响尚未阐明。因此,用1.0和2.0 μM的白花丹醌处理人胶质瘤U87和U251细胞24小时,并通过划痕伤口愈合和侵袭试验评估细胞迁移和侵袭。结果表明,白花丹醌显著抑制U87和U251细胞的迁移和侵袭,抑制MMP-2/-9的活性和表达,并抑制U87和U251细胞中转录因子Sp1的核转位。此外,白花丹醌降低了这些细胞中p-PI3K和p-Akt的水平。白花丹醌与PI3K/Akt激动剂胰岛素样生长因子-1(IGF-1)联合处理逆转了白花丹醌介导的对MMP-2/-9表达、细胞迁移和侵袭的抑制作用。这些发现表明,白花丹醌诱导的胶质瘤细胞迁移和侵袭抑制与MMP-2/-9表达和活性的下调以及PI3K/Akt信号通路激活的抑制密切相关。因此,白花丹醌可能是治疗胶质瘤的一种潜在抗侵袭剂。

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