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 ERK1/2, 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 MMPs through activation of NF-κB.
© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).