Inhibition of PLK4 might enhance the anti-tumour effect of bortezomib on glioblastoma via PTEN/PI3K/AKT/mTOR signalling pathway |
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Authors: | Jing Wang Dengpeng Ren Yan Sun Chao Xu Chunhong Wang Rui Cheng Lina Wang Guijun Jia Jinrui Ren Jiuhong Ma Yue Tu Hongming Ji |
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Affiliation: | 1. Department of neurosurgery, Shanxi academy of medical science, Shanxi Bethune Hospital, Taiyuan, China;2. Department of neurosurgery, Central Hospital of Yuncheng city, Yuncheng, China;3. Neurological intensive care unit, Special medical center of PAP, Tianjin, China;4. Department of neurosurgery, Shanxi people's hospital, Taiyuan, China |
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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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Keywords: | bortezomib glioblastoma PLK4 PTEN/PI3K/AKT/mTOR signalling pathway |
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