2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.33

PP01.33 - Wenmei Su

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The study investigates the potential of shikonin, a plant-derived compound, to overcome resistance to osimertinib, a targeted therapy for advanced non-small cell lung cancer (NSCLC). Resistance to osimertinib is a major issue in treating NSCLC, necessitating alternative therapies. <br /><br />Shikonin has shown antitumor effects in various cancers, and this study explores its impact on osimertinib resistance both in vitro (cell lines) and in vivo (mouse models). It demonstrates that shikonin enhances the effectiveness of osimertinib in resistant NSCLC cells by inducing cell death through a process called ferroptosis. Ferroptosis is a form of programmed cell death characterized by the accumulation of lipid peroxides.<br /><br />The research reveals that shikonin modulates the expression of key proteins involved in regulating cell death pathways. Specifically, shikonin attenuates the expression of HES1, a gene associated with poor prognosis in NSCLC, while promoting ATF3, leading to increased ferroptosis. The study utilizes various techniques such as cell viability assays, colony formation assays, flow cytometry, and western blotting to confirm these findings.<br /><br />In vivo experiments using mouse models confirmed that the combination of shikonin and osimertinib reduces tumor growth without significant toxicity to the host. Further proteomic and genomic analyses indicate that HES1 is overexpressed in NSCLC tissues and is strongly linked to osimertinib resistance.<br /><br />Overall, the research highlights shikonin's potential as a therapeutic agent to combat osimertinib resistance in NSCLC by promoting ferroptosis through the modulation of HES1 and ATF3 expression. This provides a promising new avenue for enhancing treatment efficacy in patients with resistant NSCLC.

Keywords

shikonin

osimertinib resistance

non-small cell lung cancer

ferroptosis

HES1

ATF3

cell death

antitumor effects

in vitro

in vivo