Anti-tumor activity of Shikonin against afatinib resistant non-small cell lung cancer via negative regulation of PI3K/Akt signaling pathway

Acquired resistance of afatinib is a significant challenge for NSCLC therapy and the mechanisms remain unclear. Aberrant activation of EGFR-dependent downstream pathways, especially 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 targeting 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 this 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.