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Visfatin Triggers the Cell Motility of Non‐Small Cell Lung Cancer via Up‐Regulation of Matrix Metalloproteinases
Author(s) -
Wang Guanghai,
Tian Wenjun,
Liu Yiqing,
Ju Ying,
Shen Yajuan,
Zhao Shengmei,
Zhang Bingchang,
Li Yu
Publication year - 2016
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12623
Subject(s) - matrix metalloproteinase , motility , metastasis , lung cancer , cancer research , medicine , pi3k/akt/mtor pathway , protein kinase b , nicotinamide phosphoribosyltransferase , cell migration , endocrinology , downregulation and upregulation , chemistry , cell , phosphorylation , cancer , signal transduction , biology , microbiology and biotechnology , enzyme , biochemistry , nad+ kinase , gene
High levels of visfatin are correlated with worse clinical prognosis of various cancers. Still, the effects and mechanisms of visfatin on progression of non‐small cell lung cancer ( NSCLC ) remain unclear. This study revealed that plasma levels of visfatin in patients with NSCLC (585 ± 287 pg/ml) were significantly ( p < 0.01) higher than those in healthy people (142 ± 61.1 pg/ml). The high level of plasma visfatin was found to be significantly ( p < 0.05) correlated with TNM stage, lymph node metastasis and distant metastasis. Visfatin treatment can increase the migration and invasion of NSCLC cells via up‐regulation of metalloproteinase‐2 ( MMP ‐2) and MMP ‐9. Both si‐ MMP ‐2 and si‐ MMP ‐9 attenuated visfatin‐induced migration of NSCLC cells. The inhibitor of NF ‐κB, while not ERK 1/2, p38‐ MAPK or PI3K/Akt, can significantly abolish visfatin‐induced migration of A549 cells and up‐regulation of MMP ‐2 and MMP ‐9. Furthermore, visfatin can increase the phosphorylation of IκBα and p65 and the transcription activities of NF ‐κB in NSCLC cells. ACHP , the inhibitor of IKK ‐β, blocked visfatin‐induced activation of p65 and up‐regulation of MMP ‐2 and MMP ‐9. Collectively, our data revealed that visfatin can trigger the in vitro migration and invasion of NSCLC cells via up‐regulation of MMP s through activation of NF ‐κB.