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Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway
Transcatheter arterial embolization (TAE) therapy has been used in the treatment of inoperable hepatocellular carcinoma (HCC). However, tumor recurrence and metastasis are common in patients after TAE, and these processes may be caused by circulating tumor cells (CTCs). Epithelial-mesenchymal transi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755195/ https://www.ncbi.nlm.nih.gov/pubmed/31432165 http://dx.doi.org/10.3892/mmr.2019.10562 |
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author | Chen, Yafei Chen, Xin Ding, Xiaojun Wang, Yingwei |
author_facet | Chen, Yafei Chen, Xin Ding, Xiaojun Wang, Yingwei |
author_sort | Chen, Yafei |
collection | PubMed |
description | Transcatheter arterial embolization (TAE) therapy has been used in the treatment of inoperable hepatocellular carcinoma (HCC). However, tumor recurrence and metastasis are common in patients after TAE, and these processes may be caused by circulating tumor cells (CTCs). Epithelial-mesenchymal transition (EMT) serves important roles in CTCs, and abnormal expression and activation of epidermal growth factor receptor (EGFR) is common in cancer cells. Afatinib is an EGFR-tyrosine kinase inhibitor (TKI). The present study aimed to investigate the effects of afatinib on EMT and tumorigenesis in HCC cells. Western blot analysis suggested that afatinib was able to effectively suppress overactivation of EGFR. Moreover, the expression levels of EMT- and metastasis-associated genes were found to be modulated by afatinib through EGFR inhibition. In addition, Cell Counting Kit-8 and Transwell assays suggested that the viability, migration and invasion of HCC cells were inhibited by afatinib through EGFR inhibition. Furthermore, the activity of the ERK signaling pathway and the expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) were decreased following treatment with afatinib in vitro. Collectively, the present results suggested that the inhibitory effects of afatinib on EMT and tumorigenesis may be associated with the ERK-VEGF/MMP9 signaling pathway. The present study provides new insights into understanding the mechanism underlying HCC and may facilitate the development of novel therapeutic strategies to treat HCC recurrence. |
format | Online Article Text |
id | pubmed-6755195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-67551952019-09-25 Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway Chen, Yafei Chen, Xin Ding, Xiaojun Wang, Yingwei Mol Med Rep Articles Transcatheter arterial embolization (TAE) therapy has been used in the treatment of inoperable hepatocellular carcinoma (HCC). However, tumor recurrence and metastasis are common in patients after TAE, and these processes may be caused by circulating tumor cells (CTCs). Epithelial-mesenchymal transition (EMT) serves important roles in CTCs, and abnormal expression and activation of epidermal growth factor receptor (EGFR) is common in cancer cells. Afatinib is an EGFR-tyrosine kinase inhibitor (TKI). The present study aimed to investigate the effects of afatinib on EMT and tumorigenesis in HCC cells. Western blot analysis suggested that afatinib was able to effectively suppress overactivation of EGFR. Moreover, the expression levels of EMT- and metastasis-associated genes were found to be modulated by afatinib through EGFR inhibition. In addition, Cell Counting Kit-8 and Transwell assays suggested that the viability, migration and invasion of HCC cells were inhibited by afatinib through EGFR inhibition. Furthermore, the activity of the ERK signaling pathway and the expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) were decreased following treatment with afatinib in vitro. Collectively, the present results suggested that the inhibitory effects of afatinib on EMT and tumorigenesis may be associated with the ERK-VEGF/MMP9 signaling pathway. The present study provides new insights into understanding the mechanism underlying HCC and may facilitate the development of novel therapeutic strategies to treat HCC recurrence. D.A. Spandidos 2019-10 2019-08-06 /pmc/articles/PMC6755195/ /pubmed/31432165 http://dx.doi.org/10.3892/mmr.2019.10562 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Chen, Yafei Chen, Xin Ding, Xiaojun Wang, Yingwei Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title | Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title_full | Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title_fullStr | Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title_full_unstemmed | Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title_short | Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh-7 cells by regulating the ERK-VEGF/MMP9 signaling pathway |
title_sort | afatinib, an egfr inhibitor, decreases emt and tumorigenesis of huh-7 cells by regulating the erk-vegf/mmp9 signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755195/ https://www.ncbi.nlm.nih.gov/pubmed/31432165 http://dx.doi.org/10.3892/mmr.2019.10562 |
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