Deoxyshikonin inhibits the proliferation, invasion, and tumor immune microenvironment in breast cancer cells by inactivating the PI3K/AKT/NF-κB pathway

BACKGROUND/OBJECTIVES: Deoxyshikonin (DSK) has been reported to inhibit tumor growth in various types of cancers, but its roles and action mechanisms in breast cancer (BC) are unclear.This study examined the anti-cancer function and mechanism of DSK in BC.MATERIALS/METHODS: MDA-MB-231 and BT549, human BC cells, were used.The cell viability and apoptosis levels were examined using Cell Counting Kit-8 experiments and flow cytometry, respectively.The expression of apoptosis-related factors (Ki-67, Bax, and Bcl-2), CD206, CD168, and proteins involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB pathway was evaluated by Western blot analysis.The cell invasion ability was determined using the Transwell experiment.The levels of interleukin (IL)-10 and transforming growth factor (TGF)-β were detected using an enzyme-linked immunosorbent assay.The in vivo functions of DSK were assessed using a xenograft mouse model.RESULTS: DSK inhibited cell proliferation, enhanced cell apoptosis, and reduced the cell invasion of MDA-MB-231 and BT549 cells.DSK also reduced the levels of CD206 and CD168 proteins, as well as IL-10 and TGF-β in phorbol 12-myristate 13-acetate-induced THP-1 cells.DSK downregulated the expression of the phosphorylated (p)-PI3K, p-AKT, and p-NF-κB proteins in cells.These effects were reversed by 740 Y-P (PI3K/AKT activator).In addition, DSK significantly reduced the tumor volume and weight in a xenograft mouse model.DSK increased the level of cell apoptosis and decreased the expression of Ki-67 and CD206 in subcutaneous tumor tissue.DSK also inactivated the PI3K/AKT/NF-κB pathway proteins.CONCLUSION: DSK inhibits the proliferation, invasion, and tumor immune microenvironment of BC cells by inactivating the PI3K/AKT/NF-κB pathway, indicating that DSK may be a potential therapeutic option for BC treatment.