Cargando…
Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The high expression of osteopontin (OPN) is an important factor that aggravates drug resistance and causes a poor prognosis in this disease. Therefore, understanding the molecular mechanism of OPN is critical for...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884967/ https://www.ncbi.nlm.nih.gov/pubmed/32063712 http://dx.doi.org/10.2147/OTT.S228437 |
_version_ | 1783474659941941248 |
---|---|
author | Cui, Jian Wang, Jun Lin, Chao Liu, Jixiang Zuo, Wei |
author_facet | Cui, Jian Wang, Jun Lin, Chao Liu, Jixiang Zuo, Wei |
author_sort | Cui, Jian |
collection | PubMed |
description | BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The high expression of osteopontin (OPN) is an important factor that aggravates drug resistance and causes a poor prognosis in this disease. Therefore, understanding the molecular mechanism of OPN is critical for the treatment and prognosis of NSCLC. METHODS: We used bioinformatics analysis to verify the expression of OPN in normal lung tissues and lung cancer tissues. Then we overexpressed and knocked down OPN in cell lines to detect cell proliferation, migration, invasion, and effects on signaling pathways. Finally, malignant progression and drug resistance induced by OPN were investigated by the wound healing assay, transwell assay, clone formation assay, and Western blot analysis. RESULTS: We verified that OPN was upregulated in NSCLC tissues, and its overexpression induced NSCLC cell proliferation, migration, and invasion via the mitogen-activated protein kinase (MAPK) pathway. Furthermore, overexpression of OPN reduced the sensitivity of NSCLC cells to cetuximab by upregulating MAPK pathway-related proteins. These results suggested that OPN promoted malignant progression and mediated drug resistance via the MAPK signaling pathway in NSCLC cells. CONCLUSION: This study reveals the important role of OPN in NSCLC cells, making it a potential target for improving chemotherapy efficiency in patients with NSCLC. |
format | Online Article Text |
id | pubmed-6884967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-68849672020-02-14 Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells Cui, Jian Wang, Jun Lin, Chao Liu, Jixiang Zuo, Wei Onco Targets Ther Original Research BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The high expression of osteopontin (OPN) is an important factor that aggravates drug resistance and causes a poor prognosis in this disease. Therefore, understanding the molecular mechanism of OPN is critical for the treatment and prognosis of NSCLC. METHODS: We used bioinformatics analysis to verify the expression of OPN in normal lung tissues and lung cancer tissues. Then we overexpressed and knocked down OPN in cell lines to detect cell proliferation, migration, invasion, and effects on signaling pathways. Finally, malignant progression and drug resistance induced by OPN were investigated by the wound healing assay, transwell assay, clone formation assay, and Western blot analysis. RESULTS: We verified that OPN was upregulated in NSCLC tissues, and its overexpression induced NSCLC cell proliferation, migration, and invasion via the mitogen-activated protein kinase (MAPK) pathway. Furthermore, overexpression of OPN reduced the sensitivity of NSCLC cells to cetuximab by upregulating MAPK pathway-related proteins. These results suggested that OPN promoted malignant progression and mediated drug resistance via the MAPK signaling pathway in NSCLC cells. CONCLUSION: This study reveals the important role of OPN in NSCLC cells, making it a potential target for improving chemotherapy efficiency in patients with NSCLC. Dove 2019-11-26 /pmc/articles/PMC6884967/ /pubmed/32063712 http://dx.doi.org/10.2147/OTT.S228437 Text en © 2019 Cui et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Cui, Jian Wang, Jun Lin, Chao Liu, Jixiang Zuo, Wei Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title | Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title_full | Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title_fullStr | Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title_full_unstemmed | Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title_short | Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells |
title_sort | osteopontin mediates cetuximab resistance via the mapk pathway in nsclc cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884967/ https://www.ncbi.nlm.nih.gov/pubmed/32063712 http://dx.doi.org/10.2147/OTT.S228437 |
work_keys_str_mv | AT cuijian osteopontinmediatescetuximabresistanceviathemapkpathwayinnsclccells AT wangjun osteopontinmediatescetuximabresistanceviathemapkpathwayinnsclccells AT linchao osteopontinmediatescetuximabresistanceviathemapkpathwayinnsclccells AT liujixiang osteopontinmediatescetuximabresistanceviathemapkpathwayinnsclccells AT zuowei osteopontinmediatescetuximabresistanceviathemapkpathwayinnsclccells |