Inhibition of PLK4 might enhance the anti‐tumour effect of bortezomib on glioblastoma via PTEN/PI3K/AKT/mTOR signalling pathway

作者：Jing Wang, Deng-Peng Ren, Yan Sun, Chao Xu, Chunhong Wang, Rui Cheng, Lina Wang, Guijun Jia, Jinrui Ren, Jiuhong Ma, Yue Tu, Hongming Ji · 发表于：Journal of Cellular and Molecular Medicine · 年份：2020 · DOI：10.1111/jcmm.14996 · 被引用次数：26 · 研究领域：Ubiquitin and proteasome pathways、Microtubule and mitosis dynamics、Multiple Myeloma Research and Treatments

Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.