Regorafenib exerts an inhibitory effect on the proliferation of human lung fibroblasts by reducing the production of several cytokines

Abstract

Abstract Background Pulmonary fibrosis is a disease that leads to respiratory failure and death. There has been little progress in therapeutic strategies for pulmonary fibrosis. There have been several reports on the cytokines associated with pulmonary fibrosis, including IL-6 and TGF-β1. Angiogenesis is one of the most important phenomena in the pathogenesis of PF. Previously, we reported the preventive effects of thalidomide against pulmonary fibrosis via the inhibition of neovascularization by angiogenic factors such as VEGF. Regorafenib is a multikinase inhibitor, which inhibits tyrosine kinase receptors such as VEGFR1-3 and TIE2. In the clinical setting, regorafenib has been widely used for anti-cancer therapy for metastatic colorectal cancer. In this study, we examined the preventive effects of regorafenib against pulmonary fibrosis. Methods We investigated whether regorafenib had an inhibitory effect on the proliferation, viability, and production of several cytokines in lung fibroblasts. Results We demonstrated an inhibitory effect of regorafenib on the proliferation and viability of lung fibroblasts. Moreover, regorafenib reduced the production of several cytokines associated with the pathogenesis of pulmonary fibrosis, including IL-6, VEGF and TGF- β1, and collagen synthesis from lung fibroblasts. Conclusions These data suggest that regorafenib may have potential clinical applications in the prevention of pulmonary fibrosis.