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Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down‐regulation of Akt/NF‐κB signaling pathway
Author(s) -
Song Jie,
Feng Liang,
Zhong Rongling,
Xia Zhi,
Zhang Li,
Cui Li,
Yan Hongmei,
Jia Xiaobin,
Zhang Zhenhai
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22471
Subject(s) - protein kinase b , tumor microenvironment , vimentin , nf κb , cancer research , mapk/erk pathway , a549 cell , biology , signal transduction , phosphorylation , pharmacology , tumor necrosis factor alpha , cytokine , epithelial–mesenchymal transition , epimedium , metastasis , microbiology and biotechnology , immunology , medicine , cell , cancer , traditional medicine , biochemistry , immunohistochemistry , herb , tumor cells , medicinal herbs , genetics
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. © 2016 Wiley Periodicals, Inc.