Unveiling the Mechanism of Action of Isoliquiritigenin in Suppressing Co- Expression of HER2 and HER3 in Breast Cancer: Implications for Clinical Application

Abstract

Background: The simultaneous expression of HER-2 and HER-3 is a crucial characteristic of HER-2-positive breast cancer, which is strongly associated with a negative prognosis. Extensive research has consistently shown the immunomodulatory, anti-tumor, and antiproliferative properties of ISL. Purpose：This study aims to assess the impact of ISL on the biological behavior of HER-2-positive breast cancer cells, while concurrently elucidating the underlying mechanisms. Study design and Methods: Cell proliferation and clonal formation capacity were evaluated through the utilization of CCK-8 and clone formation experiments, respectively, subsequent to drug intervention. The TUNEL assay was employed to detect cell apoptosis following treatment with ISL. The effects of ISL on cell invasion and migration were examined using scratch healing and TRANSWELL assays. The impact of drugs on tumorigenesis was investigated through the implementation of the subcutaneous tumor formation model of nude mice fat pad. Alterations in the PI3K-AKT signaling pathway of cells and tumor tissue were analyzed through Western blotting analysis. Results: The results of our study indicate that ISL exerts a significant inhibitory effect on tumor proliferation, clone formation, invasion, and promotes apoptosis when tested in vitro. Moreover, our in vivo experiments have provided further evidence supporting its ability to inhibit tumor cell growth. This observed effect can be attributed to the downregulation of ErbB3 expression, which is regulated by the PI3K-AKT signaling pathway. Conclusion: Through our comprehensive research efforts have revealed the intricate mechanism by which ISL effectively suppresses the co-overexpression of HER2 and HER3-positive breast cancer. By introducing innovative concepts and methodologies, our research has established laid a theoretical ground work for the transformative clinical application and utilization of ISL in the treatment of HER-2 and HER3 co-positive breast cancer.