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Novel inhibitor of TGF-β1 antagonizes TGF-β1-induced epithelial-to-mesenchymal transition in human A549 lung cancer cells

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Abstract
Transforming growth factor β1(TGF-β1), a multifunctional cytokine, is known to promote tumor invasion, metastasis and induce epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Inhibition of TGFβ signaling is a new strategy for cancer therapy. As the most cancer cells display altered or non-functional TGFβ signaling, TGFβ inhibitors have limited effects on these cells and exert their anti-tumoral activity by affecting TGF-β responsive cells. Recent study has revealed that down-regulation of cathepsin L suppresses cancer migration and invasion by inhibiting TGF-β1-mediated EMT in human A549 lung cancer cells. The aim of this study is to develop anti-TGF-β1 therapy for cancer. As suggested in recent reports, the development of a TGF-β1 inhibitor from natural compound is a key step in the development of a novel therapeutic agent. We found an improved analogue of chalcones, namely cathepsin B and L inhibitor, and investigated its anti-TGF-β1 effects in vitro. In this study, we investigated that the effects of chalcones, cathepsin B and L inhibitor on migration, invasion and EMT of human A549 lung cancer cells induced by TGF-β1. We demonstrated that chalcones blocked Smad-dependent TGF-β signaling pathway by inhibiting TGF-β1-induced Smad2 phosphorylation. Also, we observed that chalcones inhibit TGF-β1-mediated EMT.
In conclusion, development of TGF-β inhibitor was helpful for therapy of tumor growth and metastasis. As a result, our research has found new inhibitors of TGF-β1 through the inhibition of Smad activity and EMT in human lung cancer cells. TGF-β inhibitor in cancer therapy is promising and opens new challenges in clinical trial.
Author(s)
정지훈
Issued Date
2017
Awarded Date
2018-02
Type
Dissertation
URI
https://oak.ulsan.ac.kr/handle/2021.oak/6298
http://ulsan.dcollection.net/common/orgView/200000008683
Alternative Author(s)
Ji-Hoon Jeong
Affiliation
울산대학교
Department
일반대학원 의학과의과학전공
Advisor
Kyung-Chul Choi
Degree
Master
Publisher
울산대학교 일반대학원 의학과의과학전공
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medical Science > 1. Theses (Master)
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