Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway.

Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)-κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF-α-induced apoptosis. The resistance of NSCLC cell lines to TNF-α was evaluated by cell viability assay. The effect of nimotuzumab (Ni) on NSCLC cell sensitivity to TNF-α, as well as the role of NF-κB in mediating resistance to TNF-α-induced apoptosis, was explored by western blot analysis, cell viability assay, apoptosis assay and an NF-κB DNA binding assay. It was demonstrated that EGFR protein expression was markedly higher in the H292 and H1975 cell lines compared with H460 and H1299 cell lines. H292 and H1975 also exhibited significantly increased TNF-α resistance compared with H460 and H1299 cells. Low dose Ni treatment slightly reduced the viability of H292 and H1975 cells; however, combined treatment with low dose Ni and TNF-α significantly inhibited H292 and H1299 cell viability compared with H460 and H1299 cells by inducing cell apoptosis. NF-κB protein expression and activity were also inhibited by the combination treatment. TNF-α treatment alone induced apoptosis in NF-κB deficient H292 and H1975 cells, similar to the effect of combination treatment in wild type H292 and H1975 cells. The results of the present study suggest that Ni sensitizes NSCLC cell lines to TNF-α-induced cell death by inhibiting NF-κB protein expression and activation, indicating a novel mechanism by which Ni suppresses the development of NSCLC.