Additive effects of cherlerythrine chloride combination with erlotinib in human non-small cell lung cancer cells

Several studies implicate that lung cancer progression is governed by the interaction between epidermal growth factor receptor (EGFR) signaling and protein kinase C (PKC) pathways. Combined the targeting of EGFR and PKC may have an additive or synergistic effects in lung cancer treatment. The aim of this study is to explore the potential utility by inhibiting these two pathways with the combination of erlotinib and chelerythrine chloride in non-small cell lung cancer (NSCLC) cell lines. The erlotinib-less sensitive cell lines SK-MES-1 and A549 were treated with erlotinib or chelerythrine by themselves or in combination with each other. The cell viability, clonogenic survival, cell migration, invasion, cell apoptosis effects and immunoblotting were accessed in vitro. Tumor growth was evaluated in vivo. There were additive effects of chelerythrine combined with erlotinib treatment in all NSCLC cell lines, resulting in a significant decrease in cell viability, clonogenicity, migratory and invasive capabilities as well as in the induction of apoptosis. Concordantly, the combined treatment caused a significant delay in tumor growth. The treatment effectively blocked EGFR signaling through decreasing phosphorylation of downstream targets such as STAT3, ERK1/2, p38 MAPK and Bad proteins. Our study supports the functional interaction between the EGFR and PKC pathways in lung cancer and provides a clinically exploitable strategy for erlotinib-less sensitive non-small cell lung cancer patients.