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

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.

Keywords: G1 phase; glioma; invasion; migration; p21-activated kinase 1; proliferation.