Abstract
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.
Highlights
Lung cancer is the leading cause of cancer deaths worldwide [1], and the 5-year survival rate for all stages is only 15% [2]
non-small-cell lung cancer (NSCLC) can be subdivided into three categories: squamous-cell carcinoma (SQCLC), adenocarcinoma, and large-cell lung cancer
Chelerythrine chloride was purchased from Santa Cruz (Dallas, TX, USA), and erlotinib was purchased from the LC Lab (Woburn, MA, USA)
Summary
Lung cancer is the leading cause of cancer deaths worldwide [1], and the 5-year survival rate for all stages is only 15% [2]. In China, lung cancer is the leading cancer among all cancers, followed by cancers of the stomach, liver, colorectum, and breasts [3]. There are two major forms of lung cancer: non-small-cell lung cancer (NSCLC), which accounts for 85% of all lung cancers, and small-cell lung cancer, which accounts for the remaining 15%. NSCLC can be subdivided into three categories: squamous-cell carcinoma (SQCLC), adenocarcinoma, and large-cell lung cancer. Regardless of the efforts made in advanced.
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