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PAK1抑制可抑制胶质瘤细胞的增殖、迁移和侵袭。

PAK1 Inhibition Suppresses the Proliferation, Migration and Invasion of Glioma Cells.

作者信息

Yi Qinghao, Chen Tianze, Zhou Kunlin, Ma Qiang, Sun Zhiyuan, Shi Hengliang

机构信息

Central Laboratory, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

Curr Protein Pept Sci. 2023;24(2):178-189. doi: 10.2174/1389203724666221226150329.

Abstract

BACKGROUND

p21-activated kinase 1 (PAK1) is abnormally expressed in glioma, but its roles and mechanisms in glioma remain unclear. This study aims to explore the effects of PAK1 inhibition on the proliferation, migration and invasion of glioma cells.

METHODS

Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU) incorporation and colony formation assays were performed to evaluate the effects of PAK1 inhibition on the proliferation of glioma cells. The cell cycle distribution and apoptosis rate of glioma cells were explored by flow cytometry. Wound healing and Transwell assays were performed to investigate the effects of PAK1 inhibition on glioma cell migration and invasion. The orthotopic xenograft glioma model was used to probe the effect of PAK1 silencing on glioma tumor formation.

RESULTS

PAK1 inhibition arrested cells at the G1 phase and induced apoptosis of glioma cells. Moreover, the knockdown of PAK1 decreased the protein expression levels of MDM2, p38, p-p38, cyclin D1, CDK4, Bcl-2, MMP2, MMP9, and cofilin but increased the protein levels of p53, Bax, p21 and cleaved caspase-3. A xenograft glioma model confirmed that the silencing of PAK1 repressed the formation of tumors induced by U87 cell transplantation.

CONCLUSION

This study showed that PAK1 inhibition impedes the proliferation, migration, and invasion of glioma cells.

摘要

背景

p21激活激酶1(PAK1)在胶质瘤中异常表达,但其在胶质瘤中的作用及机制仍不清楚。本研究旨在探讨抑制PAK1对胶质瘤细胞增殖、迁移和侵袭的影响。

方法

采用细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)掺入及集落形成实验评估抑制PAK1对胶质瘤细胞增殖的影响。通过流式细胞术检测胶质瘤细胞的细胞周期分布及凋亡率。采用伤口愈合实验和Transwell实验研究抑制PAK1对胶质瘤细胞迁移和侵袭的影响。利用原位异种移植胶质瘤模型探究沉默PAK1对胶质瘤肿瘤形成的作用。

结果

抑制PAK1使细胞停滞于G1期并诱导胶质瘤细胞凋亡。此外,敲低PAK1可降低MDM2、p38、p-p38、细胞周期蛋白D1、细胞周期蛋白依赖性激酶4(CDK4)、Bcl-2、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)和丝切蛋白的蛋白表达水平,但可增加p53、Bax、p21和裂解的半胱天冬酶-3的蛋白水平。异种移植胶质瘤模型证实,沉默PAK1可抑制U87细胞移植诱导的肿瘤形成。

结论

本研究表明,抑制PAK1可阻碍胶质瘤细胞的增殖、迁移和侵袭。

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