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Ursolic Acid Attenuates TGF-b1-Induced Epithelial–Mesenchymal Transition in NSCLC by Targeting Integrin aVb5/MMPs Signaling

Jun Shan Ruan*†, Huan Zhou*, Lin Yang, Ling Wang*, Zong Sheng Jiang§, Hong Sun*, Shao Ming Wang*†

* Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian, P.R. China
† Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, Fujian, P.R. China
‡ Fujian Medical University Cancer Hospital, Fujian, P.R. China
§ The School of Pharmacy, Fujian Medical University, Fujian, P.R. China

Oncology Research 2019, 27(5), 593-600. https://doi.org/10.3727/096504017X15051723858706

Abstract

Transforming growth factor- 1 (TGF- 1)-induced epithelial–mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF- 1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF- 1–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- 1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF- 1-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- 1 signaling pathway-mediated integrin V 5 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- 1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.

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Cite This Article

Ruan, J. S., Zhou, H., Yang, L., Wang, L., Jiang, Z. S. et al. (2019). Ursolic Acid Attenuates TGF-b1-Induced Epithelial–Mesenchymal Transition in NSCLC by Targeting Integrin aVb5/MMPs Signaling. Oncology Research, 27(5), 593–600.



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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