Sorafenib inhibits transforming growth factor β1-Mediated Epithelial-Mesenchymal Transition and apoptosis in mouse hepatocytes

Authors

  • Yue-Lei Chen,

    1. Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Jing Lv,

    1. Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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  • Xiao-Lei Ye,

    1. Ningbo Institute of Medical Sciences, Ningbo University, Zhejiang, China
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  • Ming-Yu Sun,

    1. Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2. E-institute of Shanghai Municipal Education Committee, Shanghai, China
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  • Qin Xu,

    1. Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Cheng-Hai Liu,

    1. Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2. E-institute of Shanghai Municipal Education Committee, Shanghai, China
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  • Li-Hua Min,

    1. Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Hui-Ping Li,

    1. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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  • Ping Liu,

    Corresponding author
    1. Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2. E-institute of Shanghai Municipal Education Committee, Shanghai, China
    • Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China
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  • Xiaoyan Ding

    Corresponding author
    1. Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    • Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200031, China
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    • fax: +86-21-54921439


  • Potential conflict of interest: Nothing to report.

Abstract

Epithelial-mesenchymal transition (EMT) is a physiological process that has been recognized to occur during the progression of an increasingly large number of human diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. The activation of transforming growth factor β (TGF-β) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-β signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-β signaling. When applied to AML12 cells and primary hepatocytes, sorafenib strikingly suppressed TGF-β1-induced EMT and apoptosis. Additionally, sorafenib inhibited TGF-β1-induced signal transducer and activator of transcription 3 phosphorylation. We further present in vitro evidence that sorafenib ameliorates the proapoptotic and profibrotic effects of TGF-β1 in mouse primary hepatocytes, suggesting that this drug exerts a protective effect on hepatocytes and has therapeutic potential for the treatment of liver fibrosis. (HEPATOLOGY 2011;)

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