The integrin linked kinase promotes migration and invasion of lung cancer cell by upregulating matrix metalloproteinase-9 through nuclear factor-κB pathway / 中国综合临床

ABSTRACT

Objective To investigate the role of integrin-linked kinase (ILK) on migration and invasion of lung cancer cell by upregulating matrix metalloproteinase-9 through nuclear factor-κB (NF-κB) pathway.Methods A549 cell line were overexpressed ILK and matrix metalloproteinase-9 (MMP-9) confirmed by cell transfection,siRNA interference,cell scratch test,real-time quantitative PCR and Western Blot.Results Over-expression of ILK stimulated MMP-9 expression in lung cancer cells(P ＜ 0.01).The addition of MMP-9 inhibitor doxycycline and anti-MMP-9 neutralizing antibody significantly impaired the wound healing capacity of ILK-transfected cells(P ＜ 0.01),as well as by in vitro matrigel invasion assay (P ＜ 0.01).In addition,overexpression ILK induced phosphorylation and nuclear translocation of nuclear factor-κB subunit p65.Upregulation of MMP-9 was severely abolished by either BAY 11-7028,a specific NF-κB inhibitor,or siRNA targeted to NF-κB p65 in ILK over-expression cells.Conclusion The finding indicate that over-expression of ILK can promote the migration and invasion of lung cancer cell,and upregulate MMP-9 through the NF-κB pathway.