Anti-tumor activity of Shikonin against afatinib resistant non-small cell lung cancer via negative regulation of PI3K/Akt signaling pathway. Issue 6 (11th December 2018)

• Record Type: Journal Article
• Authors: Li, Baiying; Yuan, Zuguo; Jiang, Jin; Rao, Yuanquan
• Is Part Of: Bioscience reports. Volume 38:Issue 6(2018)
• Publication Date: 2018-12-11
• Subjects: Afatinib-resistance -- Apoptosis -- Akt -- NSCLC -- PI3K -- Shikonin; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20181693
• Languages: English
• ISSNs: 0144-8463

Abstract

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.