Erxian Decoction Enhances the Tamoxifen Sensitivity in Luminal Breast Cancer through the PI3K-AKT Signaling Pathway

Background: The primary and secondary resistance of luminal breast cancer (LBC) against endocrine therapy is a serious clinical problem. At present, it has been confirmed that Erxian Decoction can improve the sensitivity of LBC to tamoxifen (TAM), but its mechanism is not clear. The purpose of this paper is to explore the molecular mechanism that causes Erxian Decoction to increase the sensitivity of LBC to TAM.Methods: The potential targets and related pathways of Erxian Decoction inhibiting LBC were screened through bioinformatics. The small molecular compounds that could stably bind to LBC targets were determined by molecular docking. The stable interaction of the target and the small molecular compounds was revealed by the cell thermal shift assay (CETSA). Cell Counting Kit-8 (CCK-8) was used to verify the effect of Erxian Decoction and TAM on the cell activity of LBC. Flow cytometry was used to verify the effect of Erxian Decoction and TAM on the apoptosis of LBC cells. Western blot was used to detect the expression of PI3K-AKT pathway-related proteins in cells.Results: ERBB2 was screened as a potential target for the treatment of LBC. Based on molecular docking and CETSA results, the stable interaction between luteolin and ERBB2 was confirmed. CCK-8 results showed that luteolin could inhibit the cell activity of LBC, and luteolin treatment could improve the drug sensitivity of tumor cells to TAM. The results of flow cytometry showed that compared with TAM treatment alone, the addition of luteolin trefatment promoted the apoptosis level of LBC cells. Western blot results indicated that luteolin could inhibit the PI3K-AKT signal pathway by combining with ERBB2.Conclusion: Luteolin in Erxian Decoction inhibited the progression of LBC and enhanced the sensitivity of LBC to TAM by binding with ERBB2 to down-regulate the activity of the PI3K-AKT signaling pathway. This study provided theoretical support for endocrine therapy of TAM-resistant LBC patients.