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Int. J. Mol. Sci. 2014, 15(3), 4019-4030; doi:10.3390/ijms15034019
Article

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

1,†
,
2,†
,
1
,
2
,
3
 and
1,*
1 Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China 3 Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 14 January 2014 / Revised: 11 February 2014 / Accepted: 19 February 2014 / Published: 5 March 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Abstract

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.
Keywords: tamoxifen; HepG 2 cells; non-alcoholic fatty liver disease; triglyceride tamoxifen; HepG 2 cells; non-alcoholic fatty liver disease; triglyceride
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Zhao, F.; Xie, P.; Jiang, J.; Zhang, L.; An, W.; Zhan, Y. The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro. Int. J. Mol. Sci. 2014, 15, 4019-4030.

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