Berberine promotes apoptosis and inhibits the migration of oral squamous carcinoma cells through inhibition of the RAGE/PI3K/AKT/mTOR pathway

Given the high recurrence rate, elevated risk of metastasis, and drug resistance associated with oral squamous cell carcinoma (OSCC), the development of low - toxicity and highly efficient therapeutic agents has emerged as a top research priority. In this study, we conducted an in-depth investigation into the efficacy and underlying mechanism of berberine (BBR), a compound renowned for its broad anticancer activity, in the context of OSCC. Using network pharmacology, we identified 91 potential targets of BBR in OSCC, with SRC, PIK3CA, and CDC42 ranking among the top. KEGG pathway analysis indicated that the cross-targets were predominantly concentrated in signaling pathways such as PI3K/AKT, AGE-RAGE, and Ras. Molecular docking assays demonstrated that the binding energies between BBR and the core targets were all below −5 kcal/mol, signifying favorable binding interactions. Bioinformatics studies unveiled that SRC, PIK3CA, and CDC42 were highly expressed in OSCC patients and correlated with a poorer prognosis. In vitro, experiments further substantiated that BBR impeded the proliferation and migration of OSCC cells and reduced the intracellular expression levels of RAGE, p-PI3K, p-AKT, and p-mTOR proteins. Our results suggest that BBR effectively facilitates apoptosis and curbs the proliferation and migration of OSCC, potentially by suppressing the RAGE/PI3K/AKT/mTOR pathway. In summary, these findings underscore the potential of BBR as a single agent capable of exerting multi-target and multi-pathway synergistic effects on cancer cells.