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The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro
AbstractThe 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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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.View more citation formats
Zhao F, Xie P, Jiang J, Zhang L, An W, Zhan Y. The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro. International Journal of Molecular Sciences. 2014; 15(3):4019-4030.Chicago/Turabian Style
Zhao, Fei; Xie, Ping; Jiang, Jiali; Zhang, Lingqiang; An, Wei; Zhan, Yutao. 2014. "The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro." Int. J. Mol. Sci. 15, no. 3: 4019-4030.