Insights into the Molecular Mechanisms of Bushen Huoxue Decoction in Breast Cancer via Network Pharmacology and in vitro experiments

Aim:: Breast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC). Objectives:: To analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC. Materials and Methods:: Network pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC. Results:: According to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels. Conclusion:: The study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.