PI3K/AKT/mTOR通路
硼替佐米
蛋白激酶B
PTEN公司
癌症研究
基因敲除
蛋白酶体
细胞凋亡
蛋白酶体抑制剂
生物
泛素连接酶
信号转导
化学
细胞生物学
泛素
生物化学
免疫学
多发性骨髓瘤
基因
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
摘要
Abstract 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.
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