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?-Elemene inhibits the proliferation of primary human airway granulation
fibroblasts by down-regulating canonical Wnt/?-catenin pathway
#MMPMID29358311
Xue C
; Hong LL
; Lin JS
; Yao XY
; Wu DH
; Lin XP
; Zhang JM
; Zhang XB
; Zeng YM
Biosci Rep
2018[Apr]; 38
(2
): ? PMID29358311
show ga
Benign airway stenosis is a clinical challenge because of recurrent granulation
tissues. Our previous study proved that a Chinese drug, ?-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 the present study is to find out the mechanism for this
effect. We cultured fibroblasts from normal human airway tissues and human airway
granulation tissues. These cells were cultured with 160 ?g/ml normal saline (NS),
different doses of ?-elemene, or 10 ng/ml canonical Wnt/?-catenin pathway
inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression
of six molecules involved in canonical Wnt/?-catenin pathway, Wnt3a, glycogen
synthase kinase-3? (GSK-3?), ?-catenin, ?-smooth muscle actin (?-SMA),
transforming growth factor-? (TGF-?), and Collagen I (Col-I), were measured. At
last, we used canonical Wnt/?-catenin pathway activator (LiCl) to further
ascertain the mechanism of ?-elemene. Canonical Wnt/?-catenin pathway is
activated in human airway granulation fibroblasts. ?-Elemene didn't affect normal
human airway fibroblasts; however, it had a dose-responsive inhibitive effect on
the proliferation and expression of Wnt3a, non-active GSK-3?, ?-catenin, ?-SMA,
TGF-?, and Col-I of human airway granulation fibroblasts. More importantly, it
had the same effect on the expression and nuclear translocation of active
?-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be
attenuated by 10 mM LiCl. Thus, ?-elemene inhibits the proliferation of primary
human airway granulation fibroblasts by down-regulating canonical Wnt/?-catenin
pathway. This pathway is possibly a promising target to treat benign
tracheobronchial stenosis.