Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway.

Inflammatory microenvironment created by immune cells is favorable for tumor metastasis. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in inflammatory microenvironment. In this study, we sought to investigate the effects of Icariside II, a flavonol glycoside isolated from Epimedium koreanum Nakai, on A549 and H1299 cells migration in inflammatory microenvironment. At non-cytotoxic concentrations, Icariside II could inhibit invasion and EMT of A549 and H1299 cells induced by LPS-stimulated-THP-1 medium or by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Exposure to Icariside II resulted in the increment of E-cadherin, accompanied with decrement of N-cadherin, vimentin, Slug, and Snail in A549 and H1299 cells stimulated by TNF1α. Furthermore, Icariside II suppressed TNF-α-triggered nuclear translocation of NF-κB and phosphorylation of IκBα, and repressed the DNA-binding activity of NF-κB. Further data demonstrated that Akt/GSK-3β, other than MAPK signaling pathway was taking a part in the inhibitory potential of Icariside II on NF-κB activation. Importantly, Icariside II also impeded lung metastasis of A549 cells and EMT in nude mice. In conclusion, Icariside II might prohibit invasion through inactivating Akt/NF-κB pathway.