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The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro

The aim of this study was to determine the effect and mechanism of tamoxifen (TAM)-induced steatosis in vitro. HepG 2 (Human hepatocellular liver carcinoma cell line) cells were treated with different concentrations of TAM for 72 h. Steatosis of hepatocytes was determined after Oil Red O staining an...

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Autores principales: Zhao, Fei, Xie, Ping, Jiang, Jiali, Zhang, Lingqiang, An, Wei, Zhan, Yutao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975381/
https://www.ncbi.nlm.nih.gov/pubmed/24603540
http://dx.doi.org/10.3390/ijms15034019
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author Zhao, Fei
Xie, Ping
Jiang, Jiali
Zhang, Lingqiang
An, Wei
Zhan, Yutao
author_facet Zhao, Fei
Xie, Ping
Jiang, Jiali
Zhang, Lingqiang
An, Wei
Zhan, Yutao
author_sort Zhao, Fei
collection PubMed
description The aim of this study was to determine the effect and mechanism of tamoxifen (TAM)-induced steatosis in vitro. HepG 2 (Human hepatocellular liver carcinoma cell line) cells were treated with different concentrations of TAM for 72 h. Steatosis of hepatocytes was determined after Oil Red O staining and measurement of triglyceride (TG) concentration. The expressions of genes in the TG homeostasis pathway, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD), carnitine palmitoyltransferase 1 (CPT1) and microsomal triglyceride transfer protein (MTP), were examined using quantitative real-time PCR and Western blot analysis. Cell proliferation was examined using the cell counting kit-8 (CCK-8) assay. We found that hepatocytes treated with TAM had: (1) induced hepatocyte steatosis and increased hepatocyte TG; (2) upregulation of SREBP-1c, FAS, ACC, SCD and MTP mRNA expressions (300%, 600%, 70%, 130% and 160%, respectively); (3) corresponding upregulation of protein expression; and (4) no difference in HepG 2 cell proliferation. Our results suggest that TAM can induce hepatocyte steatosis in vitro and that the enhancement of fatty acid synthesis through the upregulations of SREBP-1c and its downstream target genes (FAS, ACC and SCD) may be the key mechanism of TAM-induced hepatocyte steatosis.
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spelling pubmed-39753812014-04-04 The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro Zhao, Fei Xie, Ping Jiang, Jiali Zhang, Lingqiang An, Wei Zhan, Yutao Int J Mol Sci Article The aim of this study was to determine the effect and mechanism of tamoxifen (TAM)-induced steatosis in vitro. HepG 2 (Human hepatocellular liver carcinoma cell line) cells were treated with different concentrations of TAM for 72 h. Steatosis of hepatocytes was determined after Oil Red O staining and measurement of triglyceride (TG) concentration. The expressions of genes in the TG homeostasis pathway, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD), carnitine palmitoyltransferase 1 (CPT1) and microsomal triglyceride transfer protein (MTP), were examined using quantitative real-time PCR and Western blot analysis. Cell proliferation was examined using the cell counting kit-8 (CCK-8) assay. We found that hepatocytes treated with TAM had: (1) induced hepatocyte steatosis and increased hepatocyte TG; (2) upregulation of SREBP-1c, FAS, ACC, SCD and MTP mRNA expressions (300%, 600%, 70%, 130% and 160%, respectively); (3) corresponding upregulation of protein expression; and (4) no difference in HepG 2 cell proliferation. Our results suggest that TAM can induce hepatocyte steatosis in vitro and that the enhancement of fatty acid synthesis through the upregulations of SREBP-1c and its downstream target genes (FAS, ACC and SCD) may be the key mechanism of TAM-induced hepatocyte steatosis. Molecular Diversity Preservation International (MDPI) 2014-03-05 /pmc/articles/PMC3975381/ /pubmed/24603540 http://dx.doi.org/10.3390/ijms15034019 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhao, Fei
Xie, Ping
Jiang, Jiali
Zhang, Lingqiang
An, Wei
Zhan, Yutao
The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title_full The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title_fullStr The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title_full_unstemmed The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title_short The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
title_sort effect and mechanism of tamoxifen-induced hepatocyte steatosis in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975381/
https://www.ncbi.nlm.nih.gov/pubmed/24603540
http://dx.doi.org/10.3390/ijms15034019
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