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

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.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Li B,Yuan Z,Jiang J,Rao Y

doi

10.1042/BSR20181693

subject

Has Abstract

pub_date

2018-12-11 00:00:00

issue

6

eissn

0144-8463

issn

1573-4935

pii

BSR20181693

journal_volume

38

pub_type

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