Oxymatrine inhibits cell migration and invasion in non-small-cell lung cancer by down-regulating Toll-like receptor 4 / 中国病理生理杂志

ABSTRACT

AIM:To investigate the therapeutic effect of oxymatrine on non-small-cell lung cancer(NSCLC) A549 cells and a xenograft mouse model,and to explore the underlying molecular mechanisms. METHODS:The effect of oxymatrine on the A549 cell viability was assessed by CCK-8 assay. After the A549 cells were treated with Toll-like re?ceptor 4(TLR4)stimulator lipopolysaccharide(LPS)and oxymatrine(5,10 and 15 mmol/L),the mRNA and protein ex?pression levels of TLR4 and myeloid differentiation factor 88(MyD88)were analyzed by RT-qPCR and Western blot,re?spectively. The migration and invasion abilities of the cells were measured by Transwell assay,and the mRNA and protein expression levels of matrix metalloproteinases-2(MMP-2),MMP-9 and vascular endothelial growth factor(VEGF)were also determined. A xenograft model in nude mice was utilized to evaluate the effect of oxymatrine on tumor growth. RE?SULTSOxymatrine inhibited the viability of A549 cells,decreased LPS-induced expression of TLR4,MyD88,MMP-2, MMP-9 and VEGF in A549 cells,and suppressed LPS-increased migration and invasion abilities of A549 cells. In the xe?nograft model,oxymatrine both reduced tumor growth and inhibited TLR4 expression in the tumor. CONCLUSION:Oxy?matrine exerts anti-tumor properties in NSCLC in vitro and in vivo by down-regulating the TLR4/MyD88 signaling pathway, suggesting that oxymatrine can be a potential therapeutic agent for NSCLC.