Abstract
Despite advances in cancer therapy, head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy with limited treatment options, prompting this investigation into curcumin's antitumor mechanisms through integrated network pharmacology, molecular docking, and in vitro experiments. Our comprehensive analysis identified 34 potential targets, with AKT1, EGFR, and STAT3 emerging as core targets primarily involved in regulating proliferation, apoptosis, and migration via the EGFR/STAT3 pathway. Experimental validation demonstrated curcumin's dose-dependent inhibition of viability, invasion, and migration in FaDu and CAL 27 cells, while promoting apoptosis and downregulating EGFR/STAT3 expression at both mRNA and protein levels-effects that were synergistically enhanced when combined with AG490 inhibitor. RNA-seq analysis further confirmed STAT pathway suppression as a key anticancer mechanism, collectively establishing curcumin's therapeutic potential through EGFR/STAT3 axis modulation. Overall, these preliminary network pharmacology and in vitro experimental results suggest that curcumin is a potential therapeutic agent for HNSCC and is worthy of further study. This study provides a certain theoretical basis for future clinical exploration.