Title page for etd-0718117-194840


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URN etd-0718117-194840
Author Yu-Chen Kao
Author's Email Address yubow0611@gmail.com
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Department Biological Sciences
Year 2016
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title Study the effects of Dibromotyrosine Derivative in TGF-β responsiveness
Date of Defense 2017-06-28
Page Count 81
Keyword
  • TGF-β
  • bromotyrosine derivative
  • small molecular inhibitors
  • epithelial-to-mesenchymal transition
  • Abstract The Transforming growth factor β1 (TGF-β1) is belong to transforming growth factor superfamily. Many tumor lesions process are related to TGF-β1, such as: cell proliferation, extracellular matrix secretion, cell attachment, movement, differentiation and apoptosis. TGF-β1 cell signaling via two protein receptors on membrane which are Type I TGF-β receptor (TβR-I) and Type II TGF-β receptor (TβR-II). TGF-β is activated that lead smad2/3 to phosphorylation, and p-Smad2/3 will transfer to nuclear than regulates the transcription of the target gene with other transcription factor. At cancer early stage, TGF-β will use inhibit cell proliferation and promote cell apoptosis to inhibit cancer growth, but at cancer late stage,instead, TGF-β will promote cancer cell growth, invasion, transfer and help it to escape the immune system attack. There are some small molecule inhibitors which can inhibit TGF-β cell signal transduction have great value at cancer research. Small molecule inhibitor is a powerful tool in research of signal transduction pathway interaction. In this study, we found (1′R,5′S,6′S)-2-(3′,5′- dibromo-1′,6′-dihydroxy-4′-oxocyclohex-2′-enyl) acetonitrile (DT), a bromotyrosine derivate from Pseudoceratina sp., which inhibits the TβR-I serine/threonine kinase then inhibits TGF-β downstream cell signaling. We use such as: luciferase activity assay, western blotting, wound healing assay, in vitro ALK5 kinase assay etc. to know the effect of DT on TGF-β cell signaling, and use epithelial cells to study of the inhibitory effects of DT on TGF-β-induced Smad signaling and epithelial-to-mesenchymal transition. We also confirmed the new ALK5 inhibitor can effectively inhibit TGF-β stimulate smad2/3 to phosphorylation and inhibit smad2/3 transfer to nuclear. In addition, DT also can inhibit TGF-β stimulate epithelial-to-mesenchymal transition and A549 cell metastasis. Our study showed DT can apply to treatment of fibrotic diseases and cancer in the future.
    Advisory Committee
  • Chien-Chih Chiu - chair
  • Wu, Chang-Yi - co-chair
  • Wen Zhi-Hong - co-chair
  • (Chen, Chun-Lin - advisor
  • Files
  • etd-0718117-194840.pdf
  • indicate access worldwide
    Date of Submission 2017-08-18

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