Proteasome Inhibitors Diminish c-Met Expression and Induce Cell Death in Non-Small Cell Lung Cancer Cells |
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Authors: | Yanhui Li Su Dong Arya Tamaskar Heather Wang Jing Zhao Haichun Ma Yutong Zhao |
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Institution: | * Department of Anesthesia, the First Hospital of Jilin University, Changchun, Jilin, P.R. China? Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute,
The Ohio State University, Columbus, OH, USA |
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Abstract: | Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of all
lung carcinomas. The hepatocyte growth factor receptor (c-Met) has been considered as a potential therapeutic target for NSCLC. Proteasome inhibition induces cell apoptosis and has been used as a novel therapeutic
approach for treating diseases including NSCLC; however, the effects of different proteasome inhibitors on
NSCLC have not been fully investigated. The aim of this study is to determine a precise strategy for treating
NSCLC by targeting c-Met using different proteasome inhibitors. Three proteasome inhibitors, bortezomib,
MG132, and ONX 0914, were used in this study. Bortezomib (50 nM) significantly reduced c-Met levels and
cell viability in H1299 and H441 cells, while similar effects were observed in H460 and A549 cells when a
higher concentration (~100 nM) was used. Bortezomib decreased c-Met gene expression in H1299 and H441
cells, but it had no effect in A549 and H460 cells. MG-132 at a low concentration (0.5 µM) diminished c-Met
levels in H441 cells, while neither a low nor a high concentration (~20 µM) altered c-Met levels in A549 and
H460 cells. A higher concentration of MG-132 (5 µM) was required for decreasing c-Met levels in H1299
cells. Furthermore, MG-132 induced cell death in all four cell types. Among all the four cell lines, H441 cells
expressed higher levels of c-Met and appeared to be the most susceptible to MG-132. MG-132 decreased c-Met
mRNA levels in both H1299 and H441 cells. ONX 0914 reduced c-Met levels in H460, H1299, and H441 cells
but not in A549 cells. c-Met levels were decreased the most in H441 cells treated with ONX 0914. ONX 0914
did not alter cell viability in H441; however, it did induce cell death among H460, A549, and H1299 cells. This
study reveals that different proteasome inhibitors produce varied inhibitory effects in NSCLS cell lines. |
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Keywords: | Non-small cell lung cancer (NSCLC) Proteasome inhibitor c-Met Cell viability |
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