title: The effect and mechanism of tamoxifen-induced hepatocyte steatosis in vitro.
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.
authors.affiliation: Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China. fayefly.future@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China. xpxp922@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China. jiangjl@trhos.com.
authors.forename: Jiali
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China. zhanglq@bmi.ac.cn.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. anwei@ccmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: An
authors.affiliation: Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China. yutaozhan@263.net.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Zhan
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004965:Estrogen Antagonists / Q000633:toxicity; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000633:toxicity*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004965:Estrogen Antagonists; D005227:Fatty Acids; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D013629:Tamoxifen; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase