Ursolic Acid Attenuates TGF-β1-Induced Epithelial-Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling

• Published in: Oncology research Vol. 27; no. 5; pp. 593 - 600
• Main Authors: Ruan, Jun Shan, Zhou, Huan, Yang, Lin, Wang, Ling, Jiang, Zong Sheng, Sun, Hong, Wang, Shao Ming
• Format: Journal Article
• Language: English
• Published: Elmsford, NY Cognizant Communication Corporation 07.05.2019
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Cadherins - metabolism; Carcinogenesis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Epithelial-Mesenchymal Transition; Epithelial-Mesenchymal Transition (emt); Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Metastasis; Neoplasm Invasiveness; Non-Small Cell Lung Cancer (nsclc); Receptors, Vitronectin - metabolism; Signal Transduction; Transforming Growth Factor beta1 - metabolism; Triterpenes - pharmacology; Ursolic Acid
• ISSN: 0965-0407; 1555-3906; 1555-3906
• DOI: 10.3727/096504017X15051723858706

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.