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Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells

BACKGROUND: An increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the hu...

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Autores principales: Lv, Jian, Bai, Ruidan, Wang, Li, Gao, Jiefang, Zhang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192352/
https://www.ncbi.nlm.nih.gov/pubmed/30326962
http://dx.doi.org/10.1186/s40360-018-0255-9
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author Lv, Jian
Bai, Ruidan
Wang, Li
Gao, Jiefang
Zhang, Hong
author_facet Lv, Jian
Bai, Ruidan
Wang, Li
Gao, Jiefang
Zhang, Hong
author_sort Lv, Jian
collection PubMed
description BACKGROUND: An increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the human HSC cell line, and to determine potential molecular mechanisms via the focal adhesion kinase (FAK)/ protein kinase B (Akt)/ β-catenin pathway. METHODS: LX-2 cells were stimulated with different concentration of ART (0, 12.5, 25 and 50 μg/ml) for 12, 24, 48 or 72 h, their proliferation was analyzed using the Cell Counting Kit-8 (CCK-8) assay. LX-2 cells were treated with different doses of ART (0, 12.5, 25 and 50 μg/ml) for 24 h, their apoptosis was measured using flow cytometry, the levels of mRNAs encoding collagen I or α-smooth muscle actin (α-SMA) were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the levels of key proteins in the FAK/Akt/β-catenin signaling pathway were assessed by western blotting. Specific inhibitors of FAK were added to the LX-2 cells cultures to explore the potential signaling. RESULTS: Exposing LX-2 cells to ART efficiently inhibited their proliferation, significantly promoted early apoptosis in a dose-dependent manner, and markedly downregulated the mRNA expression of α-SMA and collagen I. In addition, ART, similar to FAK inhibitor PF562271 significantly inhibited the FAK/Akt/β-catenin signaling pathway by reducing the levels of phosphorylated FAK, Akt and GSK-3β. CONCLUSIONS: Our present study shows that ART could regulate the proliferation, apoptosis and activation of LX-2. Meanwhile, the anti-fibrogenic mechanisms of ART was correlated with FAK/Akt/β-catenin pathway. Future research should verify and extend these findings, as well as explore other molecules and therefore serve as useful therapeutic targets.
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spelling pubmed-61923522018-10-22 Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells Lv, Jian Bai, Ruidan Wang, Li Gao, Jiefang Zhang, Hong BMC Pharmacol Toxicol Research Article BACKGROUND: An increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the human HSC cell line, and to determine potential molecular mechanisms via the focal adhesion kinase (FAK)/ protein kinase B (Akt)/ β-catenin pathway. METHODS: LX-2 cells were stimulated with different concentration of ART (0, 12.5, 25 and 50 μg/ml) for 12, 24, 48 or 72 h, their proliferation was analyzed using the Cell Counting Kit-8 (CCK-8) assay. LX-2 cells were treated with different doses of ART (0, 12.5, 25 and 50 μg/ml) for 24 h, their apoptosis was measured using flow cytometry, the levels of mRNAs encoding collagen I or α-smooth muscle actin (α-SMA) were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the levels of key proteins in the FAK/Akt/β-catenin signaling pathway were assessed by western blotting. Specific inhibitors of FAK were added to the LX-2 cells cultures to explore the potential signaling. RESULTS: Exposing LX-2 cells to ART efficiently inhibited their proliferation, significantly promoted early apoptosis in a dose-dependent manner, and markedly downregulated the mRNA expression of α-SMA and collagen I. In addition, ART, similar to FAK inhibitor PF562271 significantly inhibited the FAK/Akt/β-catenin signaling pathway by reducing the levels of phosphorylated FAK, Akt and GSK-3β. CONCLUSIONS: Our present study shows that ART could regulate the proliferation, apoptosis and activation of LX-2. Meanwhile, the anti-fibrogenic mechanisms of ART was correlated with FAK/Akt/β-catenin pathway. Future research should verify and extend these findings, as well as explore other molecules and therefore serve as useful therapeutic targets. BioMed Central 2018-10-16 /pmc/articles/PMC6192352/ /pubmed/30326962 http://dx.doi.org/10.1186/s40360-018-0255-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lv, Jian
Bai, Ruidan
Wang, Li
Gao, Jiefang
Zhang, Hong
Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title_full Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title_fullStr Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title_full_unstemmed Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title_short Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells
title_sort artesunate may inhibit liver fibrosis via the fak/akt/β-catenin pathway in lx-2 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192352/
https://www.ncbi.nlm.nih.gov/pubmed/30326962
http://dx.doi.org/10.1186/s40360-018-0255-9
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