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Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway

Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investi...

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Autores principales: Zhang, Rui, Wang, Ge, Zhang, Peng‐Fei, Zhang, Jing, Huang, Yan‐Xia, Lu, Yun‐Min, Da, Wei, Sun, Qun, Zhu, Jin‐Shui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431127/
https://www.ncbi.nlm.nih.gov/pubmed/27957827
http://dx.doi.org/10.1111/jcmm.13043
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author Zhang, Rui
Wang, Ge
Zhang, Peng‐Fei
Zhang, Jing
Huang, Yan‐Xia
Lu, Yun‐Min
Da, Wei
Sun, Qun
Zhu, Jin‐Shui
author_facet Zhang, Rui
Wang, Ge
Zhang, Peng‐Fei
Zhang, Jing
Huang, Yan‐Xia
Lu, Yun‐Min
Da, Wei
Sun, Qun
Zhu, Jin‐Shui
author_sort Zhang, Rui
collection PubMed
description Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investigate the correlation of dual‐specificity phosphatase 4 (DUSP4) expression with clinicopathologic features and overall survival in patients with GC and explore the effects of sanguinarine on tumour growth and invasion in GC cells (SGC‐7901 and HGC‐27) and underlying molecular mechanisms. Immunohistochemical analysis showed that decreased DUSP4 expression was associated with the sex, tumour size, depth of invasion and distant metastasis in patients with GC. Functional experiments including CCK‐8, Transwell and flow cytometry analysis indicated that sanguinarine or DUSP4 overexpression inhibited GC cell viability and invasive potential, and induced cell apoptosis and cycle arrest in S phase, but DUSP4 knockdown attenuated the antitumour activity of sanguinarine. Further observation demonstrated that sanguinarine up‐regulated the expression of DUSP4 and Bcl‐2‐associated X protein (Bax), but down‐regulated phosphorylated extracellular signal‐regulated kinase (p‐ERK), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP‐2) and B‐cell lymphoma 2 (Bcl‐2) expression. Taken together, our findings indicate that sanguinarine inhibits growth and invasion of GC cells through regulation of the DUSP4/ERK pathway, suggesting that sanguinarine may have potential for use in GC treatment.
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spelling pubmed-54311272017-06-01 Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway Zhang, Rui Wang, Ge Zhang, Peng‐Fei Zhang, Jing Huang, Yan‐Xia Lu, Yun‐Min Da, Wei Sun, Qun Zhu, Jin‐Shui J Cell Mol Med Original Articles Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investigate the correlation of dual‐specificity phosphatase 4 (DUSP4) expression with clinicopathologic features and overall survival in patients with GC and explore the effects of sanguinarine on tumour growth and invasion in GC cells (SGC‐7901 and HGC‐27) and underlying molecular mechanisms. Immunohistochemical analysis showed that decreased DUSP4 expression was associated with the sex, tumour size, depth of invasion and distant metastasis in patients with GC. Functional experiments including CCK‐8, Transwell and flow cytometry analysis indicated that sanguinarine or DUSP4 overexpression inhibited GC cell viability and invasive potential, and induced cell apoptosis and cycle arrest in S phase, but DUSP4 knockdown attenuated the antitumour activity of sanguinarine. Further observation demonstrated that sanguinarine up‐regulated the expression of DUSP4 and Bcl‐2‐associated X protein (Bax), but down‐regulated phosphorylated extracellular signal‐regulated kinase (p‐ERK), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP‐2) and B‐cell lymphoma 2 (Bcl‐2) expression. Taken together, our findings indicate that sanguinarine inhibits growth and invasion of GC cells through regulation of the DUSP4/ERK pathway, suggesting that sanguinarine may have potential for use in GC treatment. John Wiley and Sons Inc. 2016-12-13 2017-06 /pmc/articles/PMC5431127/ /pubmed/27957827 http://dx.doi.org/10.1111/jcmm.13043 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhang, Rui
Wang, Ge
Zhang, Peng‐Fei
Zhang, Jing
Huang, Yan‐Xia
Lu, Yun‐Min
Da, Wei
Sun, Qun
Zhu, Jin‐Shui
Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title_full Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title_fullStr Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title_full_unstemmed Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title_short Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway
title_sort sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the dusp4/erk pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431127/
https://www.ncbi.nlm.nih.gov/pubmed/27957827
http://dx.doi.org/10.1111/jcmm.13043
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