Astragaloside–Brucea Javanica Oil Nanoemulsion Regulates Glycolysis in Oral Squamous Cell Carcinoma Through AURKA-Mediated PI3K/AKT/HIF-1α Pathway

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and glycolysis plays a key role in its development. In the early stages of the study, we prepared a nanoemulsion containing Astragaloside IV (AS-IV) and Brucea javanica oil (BJO). This Astragaloside–Brucea Javanica Oil nanoemulsion (AS/BJO-NE) demonstrated a stronger inhibitory effect on the proliferation, invasion, and migration of OSCC cells than either AS-IV or BJO alone. Preliminary experiments also showed that AS/BJO-NEs inhibited glycolysis in OSCC cells. The aim of this study was to investigate how AS/BJO-NEs act against OSCC by targeting glycolysis-related genes and pathways. Methods: Prepare AS/BJO-NEs and determine their particle size, PDI, and potential. Network pharmacology and bioinformatics analysis were employed to identify the core genes and pathways of AS/BJO-NEs involved in regulating glycolysis in OSCC. In vitro and vivo experiments were performed to investigate the effects of AS/BJO-NEs on OSCC tumor development and core gene expression levels. Results: Aurora kinase A (AURKA) is a critical target through which AS/BJO-NEs regulate glycolytic metabolism in OSCC. Combined in vitro and in vivo experiments revealed that AS/BJO-NEs suppress glycolysis-related enzymes HK2 and PKM2 through the AURKA/PI3K/AKT/HIF-1α signaling axis, consequently inhibiting OSCC proliferation, invasion, metastasis, and subcutaneous tumorigenesis. Conclusions: Bioinformatics analysis combined with in vitro and vivo experiments demonstrated that AS/BJO-NEs downregulate OSCC glycolysis via the AURKA/PI3K/AKT/HIF-1α pathway at the metabolic level, thereby inhibiting OSCC progression. Elucidation of this mechanism provides theoretical support and experimental evidence for the anti-OSCC effects of AS/BJO-NEs.