Epidermal growth factor-mediated NF-kappaB activation promotes uPA expression and invasiveness in pancreatic cancer cells / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To determine the effect of EGF on the invasiveness of pancreatic cancer cells and its related regulatory mechanism.</p><p><b>METHODS</b>The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay. The expression of uPA was assayed by Western blot and RT-PCR. The activity of NF-kappaB was examined by EMSA.</p><p><b>RESULTS</b>EGF significantly increased the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. Increased invasiveness was associated with the induction of uPA at both mRNA and protein levels. Furthermore, EGF stimulated the NF-kappaB binding activity, and pretreatment of cells with a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated EGF-induced NF-kappaB activation. Subsequently, the EGF-induced uPA expression and invasiveness were also inhibited by NF-kappaB inhibitor.</p><p><b>CONCLUSION</b>Our findings indicated that NF-kappaB-mediated up-regulation of uPA expression is responsible for EGF-induced invasiveness in pancreatic cancer cells, and implicate that such anti-NF-kappaB therapy with NF-kappaB inhibitors may contribute to the reduction of invasiveness of pancreatic cancer.</p>