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Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling

BACKGROUND: Statins, which are used to lower blood cholesterol levels by inhibiting HMG-CoA reductase, have shown anticancer effects in many cancer cells. However, the role of statins in gastric cancer remains unclear. This study aims to investigate whether the statins could antagonize progression o...

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Autores principales: Liu, Qing, Xia, Hongwei, Zhou, Sheng, Tang, Qiulin, Zhou, Jitao, Ren, Min, Bi, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074824/
https://www.ncbi.nlm.nih.gov/pubmed/32210573
http://dx.doi.org/10.2147/OTT.S237693
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author Liu, Qing
Xia, Hongwei
Zhou, Sheng
Tang, Qiulin
Zhou, Jitao
Ren, Min
Bi, Feng
author_facet Liu, Qing
Xia, Hongwei
Zhou, Sheng
Tang, Qiulin
Zhou, Jitao
Ren, Min
Bi, Feng
author_sort Liu, Qing
collection PubMed
description BACKGROUND: Statins, which are used to lower blood cholesterol levels by inhibiting HMG-CoA reductase, have shown anticancer effects in many cancer cells. However, the role of statins in gastric cancer remains unclear. This study aims to investigate whether the statins could antagonize progression of gastric cancer cells and tried to find the molecule mechanism. METHODS: Effects of simvastatin on the morphology, proliferation, migration, apoptosis, and invasion of gastric cancer cells were detected and compared. Western blotting, cell viability assay, fluorescence, and transfection were employed to study the molecule mechanism of the effects and the interaction between YAP and β-catenin signaling. RESULTS: Simvastatin could inhibit proliferation, migration and invasion, and promote the apoptosis in gastric cancer cells. Mechanistic studies showed that simvastatin treatment could inhibit the expression of β-catenin and the activity of YAP and the downstream targets of YAP and β-catenin in gastric cancer cells. Moreover, we found that YAP and β-catenin could form a positive feedback loop in gastric cancer cells. Further investigation revealed that simvastatin mainly acted through by inhibiting the activity of RhoA to inhibit YAP and β-catenin, and the geranylgeranyl pyrophosphate pathway mediated this regulation. CONCLUSION: Statins represent a promising therapeutic option for gastric cancer by simultaneously targeting YAP and β-catenin signaling.
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spelling pubmed-70748242020-03-24 Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling Liu, Qing Xia, Hongwei Zhou, Sheng Tang, Qiulin Zhou, Jitao Ren, Min Bi, Feng Onco Targets Ther Original Research BACKGROUND: Statins, which are used to lower blood cholesterol levels by inhibiting HMG-CoA reductase, have shown anticancer effects in many cancer cells. However, the role of statins in gastric cancer remains unclear. This study aims to investigate whether the statins could antagonize progression of gastric cancer cells and tried to find the molecule mechanism. METHODS: Effects of simvastatin on the morphology, proliferation, migration, apoptosis, and invasion of gastric cancer cells were detected and compared. Western blotting, cell viability assay, fluorescence, and transfection were employed to study the molecule mechanism of the effects and the interaction between YAP and β-catenin signaling. RESULTS: Simvastatin could inhibit proliferation, migration and invasion, and promote the apoptosis in gastric cancer cells. Mechanistic studies showed that simvastatin treatment could inhibit the expression of β-catenin and the activity of YAP and the downstream targets of YAP and β-catenin in gastric cancer cells. Moreover, we found that YAP and β-catenin could form a positive feedback loop in gastric cancer cells. Further investigation revealed that simvastatin mainly acted through by inhibiting the activity of RhoA to inhibit YAP and β-catenin, and the geranylgeranyl pyrophosphate pathway mediated this regulation. CONCLUSION: Statins represent a promising therapeutic option for gastric cancer by simultaneously targeting YAP and β-catenin signaling. Dove 2020-03-09 /pmc/articles/PMC7074824/ /pubmed/32210573 http://dx.doi.org/10.2147/OTT.S237693 Text en © 2020 Liu 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
Liu, Qing
Xia, Hongwei
Zhou, Sheng
Tang, Qiulin
Zhou, Jitao
Ren, Min
Bi, Feng
Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title_full Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title_fullStr Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title_full_unstemmed Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title_short Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and β-Catenin Signaling
title_sort simvastatin inhibits the malignant behaviors of gastric cancer cells by simultaneously suppressing yap and β-catenin signaling
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074824/
https://www.ncbi.nlm.nih.gov/pubmed/32210573
http://dx.doi.org/10.2147/OTT.S237693
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