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lüll The effect and mechanism of tamoxifen-induced hepatocyte steatosis in vitro Zhao F; Xie P; Jiang J; Zhang L; An W; Zhan YInt J Mol Sci 2014[Mar]; 15 (3): 4019-30The 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 gamma (PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha), 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.|Acetyl-CoA Carboxylase/genetics/metabolism[MESH]|Blotting, Western[MESH]|Carcinoma, Hepatocellular/genetics/metabolism/pathology[MESH]|Cell Proliferation/drug effects[MESH]|Cell Survival/drug effects/genetics[MESH]|Estrogen Antagonists/toxicity[MESH]|Fatty Acid Synthases/genetics/metabolism[MESH]|Fatty Acids/*biosynthesis[MESH]|Fatty Liver/chemically induced/genetics/metabolism[MESH]|Gene Expression/drug effects[MESH]|Hep G2 Cells[MESH]|Hepatocytes/*drug effects/metabolism/pathology[MESH]|Humans[MESH]|Lipid Metabolism/genetics[MESH]|Liver Neoplasms/genetics/metabolism/pathology[MESH]|Reverse Transcriptase Polymerase Chain Reaction[MESH]|Stearoyl-CoA Desaturase/genetics/metabolism[MESH]|Sterol Regulatory Element Binding Protein 1/genetics/metabolism[MESH]|Tamoxifen/*toxicity[MESH]|Triglycerides/*metabolism[MESH] |