title: Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway.
abstract: 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.
authors: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.|Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Jie
authors: J
authors: Song
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Liang
authors: L
authors: Feng
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Rongling
authors: R
authors: Zhong
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Zhi
authors: Z
authors: Xia
authors: Clinical Laboratory, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Li
authors: L
authors: Zhang
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Li
authors: L
authors: Cui
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Hongmei
authors: H
authors: Yan
authors: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.|Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Xiaobin
authors: X
authors: Jia
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors: Zhenhai
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D034181:Epimedium / Q000737:chemistry; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D016328:NF-kappa B / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C060988:baohuoside I; D051057:Proto-Oncogene Proteins c-akt
keywords: Icariside II; cell invasion; epithelial-mesenchymal transition; inflammatory microenvironment; tumor necrosis factor-α