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Tat-NTS 通过抑制膜联蛋白 A1 的核转位抑制神经胶质瘤细胞的增殖、迁移和侵袭。

Tat-NTS Suppresses the Proliferation, Migration and Invasion of Glioblastoma Cells by Inhibiting Annexin-A1 Nuclear Translocation.

机构信息

Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli St., Jiangan District, Wuhan, 430014, China.

Department of Respiration, The Children's Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430015, China.

出版信息

Cell Mol Neurobiol. 2022 Nov;42(8):2715-2725. doi: 10.1007/s10571-021-01134-y. Epub 2021 Aug 3.

Abstract

Prevention of the nuclear translocation of ANXA1 with Tat-NTS was recently reported to alleviate neuronal injury and protect against cerebral stroke. However, the role that Tat-NTS plays in the occurrence and development of gliomas still needs to be elucidated. Therefore, human glioblastoma (GB) cells were treated with various concentrations of Tat-NTS for 24 h, and cell proliferation, migration and invasion were assessed with CCK-8 and Transwell assays. The nuclear translocation of ANXA1 was evaluated by subcellular extraction and immunofluorescence, and protein expression levels were detected by Western blot analysis. In addition, the activity of MMP-2/9 was measured by gelatin zymography. The results revealed that Tat-NTS significantly inhibited the nuclear translocation of ANXA1 in U87 cells and inhibited the proliferation, migration and invasion of GB cells. Tat-NTS also suppressed cell cycle regulatory proteins and MMP-2/-9 activity and expression. Moreover, Tat-NTS reduced the level of p-p65 NF-κB in U87 cells. These results suggest that the Tat-NTS-induced inhibition of GB cell proliferation, migration and invasion is closely associated with the induction of cell cycle arrest, downregulation of MMP-2/-9 expression and activity and suppression of the NF-κB signaling pathway. Thus, Tat-NTS may be a potential chemotherapeutic agent for the treatment of GB.

摘要

最近有研究报道,使用 Tat-NTS 预防 ANXA1 的核易位可以减轻神经元损伤并预防脑卒。然而,Tat-NTS 在胶质瘤的发生和发展中所起的作用仍需要进一步阐明。因此,用不同浓度的 Tat-NTS 处理人神经胶质瘤(GB)细胞 24 h,通过 CCK-8 和 Transwell 实验评估细胞增殖、迁移和侵袭能力。通过亚细胞提取和免疫荧光评估 ANXA1 的核易位,通过 Western blot 分析检测蛋白表达水平。此外,通过明胶酶谱法测量 MMP-2/9 的活性。结果表明,Tat-NTS 可显著抑制 U87 细胞中 ANXA1 的核易位,并抑制 GB 细胞的增殖、迁移和侵袭。Tat-NTS 还抑制细胞周期调节蛋白和 MMP-2/-9 的活性和表达。此外,Tat-NTS 降低了 U87 细胞中 p-p65 NF-κB 的水平。这些结果表明,Tat-NTS 诱导的 GB 细胞增殖、迁移和侵袭抑制与细胞周期阻滞、MMP-2/-9 表达和活性下调以及 NF-κB 信号通路抑制密切相关。因此,Tat-NTS 可能是治疗神经胶质瘤的一种有潜力的化疗药物。

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