Sorafenib Inhibits Transforming Growth Factor β1-Mediated Epithelial-Mesenchymal Transition and Apoptosis in Mouse Hepatocytes

被引：95

作者：

Chen, Yue-Lei ^{[1
]}

Lv, Jing ^{[2
]}

Ye, Xiao-Lei ^{[3
]}

Sun, Ming-Yu ^{[2
,4
]}

Xu, Qin ^{[1
]}

Liu, Cheng-Hai ^{[2
,4
]}

Min, Li-Hua ^{[1
]}

Li, Hui-Ping ^{[5
]}

Liu, Ping ^{[2
,4
]}

Ding, Xiaoyan ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci SIBS, Inst Biochem & Cell Biol, Key Lab Mol Cell Biol, Shanghai 200031, Peoples R China

[2] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Liver Dis, Key Lab Liver & Kidney Dis,Minist Educ, Shanghai 201203, Peoples R China

[3] Ningbo Univ, Ningbo Inst Med Sci, Ningbo, Zhejiang, Peoples R China

[4] Shanghai Municipal Educ Comm, E Inst, Shanghai, Peoples R China

[5] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China

来源：

HEPATOLOGY | 2011年 / 53卷 / 05期

基金：

中国国家自然科学基金;

关键词：

TGF-BETA; LIVER FIBROSIS; MECHANISMS; FIBROGENESIS; SUPPRESSION; ROLES; CELLS;

D O I：

10.1002/hep.24254

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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 beta (TGF-beta) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-beta signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-beta signaling. When applied to AML12 cells and primary hepatocytes, sorafenib strikingly suppressed TGF-beta 1-induced EMT and apoptosis. Additionally, sorafenib inhibited TGF-beta 1-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-beta 1 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;53:1708-1718)

引用

页码：1708 / 1718

页数：11

共 39 条

[1]

Transforming growth factor β and the liver [J].