Open AccessUrsolic Acid Attenuates TGF-β1-Induced Epithelial‐Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling
Author(s) -
Jian Ruan,
Huan Zhou,
Lin Yang,
Ling Wang,
Zhen Jiang,
Hong Sun,
Shaoming Wang
Publication year - 2019
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504017x15051723858706
Subject(s) - ursolic acid , epithelial–mesenchymal transition , cancer research , signal transduction , metastasis , transforming growth factor , integrin , cell migration , mesenchymal stem cell , cell growth , biology , chemistry , cell , microbiology and biotechnology , medicine , cancer , biochemistry , botany
Transforming growth factor-β1 (TGF-β1)-induced epithelial‐mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1‐integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway-mediated integrin αVβ5 expression, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.