Epithelial-mesenchymal transition (EMT) has been reported to play pivotal roles in
tumor invasion and
metastasis. Inhibition of EMT may exert beneficial effects in regulating
metastasis.
Oridonin (ORI), an active
diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti-metastatic agent. However, the possible involvement of ORI in the EMT in
malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16-F10
melanoma cells. The transforming growth factor-β1 (TGF-β1)-induced EMT was also inhibited in ORI-treated cells, as reflected in the upregulation of
E-cadherin, and downregulation of
vimentin and Snail. Similar results were observed in A375 and B16-F10
melanoma cells treated with ORI. Furthermore, pre-treatment with ORI blocked the TGF-β1-induced
phosphoinositide 3-kinase (PI3K)/AKT
serine/threonine kinase (Akt)/
glycogen synthase kinase (GSK)-3β signaling pathway activation. These effects mimicked
PI3 kinase inhibitor
LY294002 treatment. ORI interfered with the PI3K/Akt/GSK-3β pathway, and reversed TGF-β1-induced EMT, which suppressed the invasion and
metastasis of
melanoma cells. Taken together, the present study demonstrated that ORI inhibits
melanoma cells migration, invasion, and adhesion and TGF-β1-induced EMT through the PI3K/Akt/GSK-3β signaling pathway. These findings suggest that ORI is a promising anti-
metastasis agent for
melanoma.