Prof. Transient receptor potential vanilloid 4 promotes the growth of non-small cell lung cancer by regulating Foxp3 TRPV4 promote NSCLC development

• Published in: Acta biochimica polonica
• Main Authors: Pu, Jiang-tao, Zhang, Tao, He, Kai-ming, Zhang, Deng-guo, Teng, Zhang-yu, Wu, Yun-fei
• Format: Journal Article
• Language: English
• Published: 07.01.2022
• ISSN: 0001-527X; 1734-154X
• DOI: 10.18388/abp.2020_5614

Objective(s): Transient receptor potential vanilloid 4 (TRPV4) participates in malignant tumor. However, the role of TRPV4 in non-small cell lung cancer (NSCLC) remains unclear. In this study, we demonstrated TRPV4 was upregulated in NSCLC tissues and NSCLC cell lines. Materials and Methods: TRPV4 level in the NSCLC patients and cell lines were detected, and its function was studied both in vivo and vitro. Results: The level of TRPV4 showed a positive correlation with tumor size of NSCLC patients. Activation TRPV4 by agonist GSK1016790A promoted cell proliferation and decreased apoptosis in A549 cells, and these effects were enhanced when the cells have overexpressed TRPV4. Moreover, GSK1016790A induced inhibitory effects on apoptosis of A549 cells was impaired when GSK1016790A used together with TRPV4 selective antagonist HC-067047, or impaired when the cells have already downregulated TRPV4 expression by TRPV4 siRNA. In vivo study, pharmacological inhibition of TRPV4 prevented A549 cells transplanted tumor growth. It was showed Foxp3 level was significantly increased in the NSCLC tissues, and showed a positive correlation with the level of TRPV4. Deactivation of TRPV4 using TRPV4 siRNA or HC-067047 significantly reduced expression of Foxp3 in GSK1016790A treated NSCLC cells. Moreover, downregulation Foxp3 by transfection of Foxp3 siRNA significantly impaired TRPV4 induced NSCLC cells proliferations in vitro. Conclusions: Antitumor effects caused by TRPV4 inhibition in NSCLC might be attributed to the suppression of Foxp3 which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 may be a promising option for NSCLC treatment.