Transient receptor potential vanilloid 4 promotes the growth of non-small cell lung cancer by regulating Foxp3

Abstract

Transient receptor potential vanilloid 4 (TRPV4) functions in malignant tumours. However, the role of TRPV4 in non-small cell lung cancer (NSCLC) remains unclear. In this study, we demonstrated that TRPV4 expression was upregulated in NSCLC tissues and cell lines. The TRPV4 levels in NSCLC patients and cell lines were detected, and the function of TRPV4 was studied both in vivo and in vitro. The level of TRPV4 showed a positive correlation with the tumour size in NSCLC patients. Activation of TRPV4 by the agonist GSK1016790A promoted cell proliferation and decreased apoptosis in A549 cells, and these effects were enhanced when the cells overexpressed TRPV4. Moreover, the inhibitory effects of GSK1016790A on the apoptosis of A549 cells were impaired when GSK1016790A was used together with the TRPV4 selective antagonist HC-067047 or when the cells were transfected with TRPV4 siRNA to downregulate TRPV4 expression. In an in vivo study, pharmacological inhibition of TRPV4 prevented A549 cell-derived transplanted tumour growth. The Foxp3 levels were significantly increased in NSCLC tissues and showed a positive correlation with the TRPV4 levels. Inhibition of TRPV4 using TRPV4 siRNA or HC-067047 significantly reduced the expression of Foxp3 in GSK1016790A-treated NSCLC cells. Moreover, downregulation of Foxp3 by transfection with Foxp3 siRNA significantly impaired TRPV4-induced NSCLC cell proliferation in vitro. The antitumour effects caused by TRPV4 inhibition in NSCLC might be attributed to the suppression of Foxp3, which subsequently induced cell apoptosis. Thus, pharmacological inhibition of TRPV4 may be a promising option for NSCLC treatment.