Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Pathology / 病理學科所
  4. Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition
 
  • Details

Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition

Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
112
Journal Issue
23
Pages
7243-7248
Date Issued
2015
Author(s)
TUNG-HUNG SU  
Shiau C.-W
Jao P
CHEN-HUA LIU  
CHUN-JEN LIU  
Tai W.-T
YUNG-MING JENG  
HUNG-CHIH YANG  
TAI-CHUNG TSENG  
HSIANG-PO HUANG  
Cheng H.-R
PEI-JER CHEN  
Chen K.-F
JIA-HORNG KAO  
DING-SHINN CHEN  
DOI
10.1073/pnas.1507499112
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983718348&doi=10.1073%2fpnas.1507499112&partnerID=40&md5=7e9fa2863eb624e1ca20e528ea47f0de
https://scholars.lib.ntu.edu.tw/handle/123456789/473313
Abstract
Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in vivo and in vitro with special focus on the STAT3 pathway in hepatic stellate cells (HSCs). The clinical role of STAT3 in chronic hepatitis B (CHB) was also investigated. Experimental fibrosis mouse models were established by thioacetamide injection and bile duct ligation in Balb/C mice and treated with sorafenib and SC-1. Rat and human HSCs were used for mechanistic investigations. Forty CHB patients were enrolled to quantify the hepatic phospho-STAT3 (p-STAT3) levels and correlated with liver fibrosis. Both sorafenib and SC-1 ameliorated liver fibrosis in vivo and promoted HSC apoptosis in vitro. p-STAT3 and downstream signals were down-regulated after sorafenib and SC-1 treatment in HSC. STAT3 overexpression in HSC enhanced cell proliferation and undermined the apoptotic effects of sorafenib and SC-1, whereas STAT3-specific inhibition promoted HSC apoptosis. Sorafenib and SC-1 activated Src-homology protein tyrosine phosphatase-1 (SHP-1) and STAT3 inhibition followed. Of particular interest, in CHB patients with advanced liver fibrosis, p-STAT3 in HSC was significantly overexpressed and positively correlated with the severity of liver fibrosis and plasma IL-6 levels. In conclusion, sorafenib and SC-1 ameliorate liver fibrosis through STAT3 inhibition in HSC and STAT3 may potentially serve as a promising fibrotic biomarker and target in liver fibrosis. SHP-1 phosphatase-directed STAT3 inhibition may represent a previously unidentified strategy for antifibrotic drug discovery. ? 2015 PNAS.
SDGs

[SDGs]SDG3

Other Subjects
3 (6 bromo 2 pyridinyl) 2 cyano n (1 phenylethyl)acrylamide; alpha smooth muscle actin; collagen; cyclin D1; interleukin 6; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein mcl 1; protein tyrosine phosphatase; protein tyrosine phosphatase SHP 1; Raf protein; sc 1; sorafenib; src homology protein tyrosine phosphatase 1; STAT3 protein; thioacetamide; unclassified drug; vanadate sodium; carbanilamide derivative; nicotinamide; sorafenib; STAT3 protein; STAT3 protein, human; animal cell; animal experiment; animal model; apoptosis; Article; bile duct ligation; cell death; cell proliferation; cell viability; chronic hepatitis B; clinical article; colony formation; comparative study; controlled study; disease severity; down regulation; enzyme activity; experimental liver fibrosis; flow cytometry; histopathology; human; human cell; human tissue; in vitro study; in vivo study; liver biopsy; liver fibrosis; male; mouse; nonhuman; priority journal; protein expression; rat; stellate cell; upregulation; Western blotting; analogs and derivatives; animal; antagonists and inhibitors; Bagg albino mouse; cell line; chemistry; drug effects; liver cirrhosis; Mus; Rattus; Animals; Cell Line; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Niacinamide; Phenylurea Compounds; Rats; STAT3 Transcription Factor
Publisher
National Academy of Sciences
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science