β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway

Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of this study is to find out the mechanism. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 ug/ml NS, different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (DKK-1). The proliferation rate of cells and the expression of six molecules invoveled in canonical Wnt/β-catenin pathway, Wnt3a, GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I, were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl), to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn't affect normal human airway fibroblasts, however had a dose-responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by downregulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.