Abstract
Acquired resistance of afatinib is a significant challenge for non-small cell lung cancer (NSCLC) therapy and the mechanisms remain unclear. Aberrant activation of epidermal growth factor receptor (EGFR)-dependent downstream pathways, especially phosphatidylinositol-3-kinases/protein kinase B (PI3K/Akt) signaling pathway has been reported to be involved in the occurrence of afatinib resistance. Developing effective anti-cancer agents to overcome afatinib resistance by targetting PI3K/Akt signaling pathway will be a potential strategy for NSCLC treatment. Shikonin is a naphthoquinone compound isolated from the roots of Lithospermum erythrorhizon. In the present study, the anti-cancer activity of Shikonin was evaluated on afatinib-resistant NSCLC in vitro and in vivo. The data showed that Shikonin inhibited the proliferation and induced apoptosis of afatinib-resistant NSCLC cell line by activating apoptosis signaling pathway and negatively regulating PI3K/Akt signaling pathway. These results revealed that Shikonin was a potential apoptosis inducer in afatinib-resistant NSCLC and a promising candidate for treating patients clinically.
Highlights
Lung cancer is the most common cause of cancer-related deaths in the world and nearly 80% of lung cancer cases are non-small cell lung cancer (NSCLC)
Epidermal growth factor receptor (EGFR) mutations are involved in the progression of NSCLC and the mutations of EGFR are most frequently found in lung adenocarcinoma cells
The result revealed that Shikonin-mediated suppression of cell viability in afatinib-resistant NSCLC cells was correlated with enhanced apoptosis induction
Summary
Lung cancer is the most common cause of cancer-related deaths in the world and nearly 80% of lung cancer cases are non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are involved in the progression of NSCLC and the mutations of EGFR are most frequently found in lung adenocarcinoma cells. Afatinib provided prolonged survival when compared with chemotherapy, as well as gefitinib as first-line therapy in lung adenocarcinoma and erlotinib in the second-line setting in squamous cell carcinoma (SCC) [5,6,7]. Fibroblast growth factor receptors 1 (FGFR1) activation, amplified KRAS or NRAS expression, contributed to c 2018 The Author(s).
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