Quercetin suppresses the malignant phenotypes and epithelial-mesenchymal transition in head and neck squamous cell carcinoma cells by regulating the PI3K/AKT signaling pathway

Background Quercetin (Que) has demonstrated anticancer potential against head and neck squamous cell carcinoma (HNSCC), but its role in regulating epithelial-mesenchymal transition (EMT) through the PI3K/AKT signaling remains incompletely understood. This study aimed to investigate whether Que can suppress the malignant phenotypes and EMT-related changes in HNSCC cells through regulating the PI3K/AKT pathway. Methods Cal27 and FaDu cells were treated with cell-line-specific Que concentrations. Cell viability, colony formation, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays. Western blotting was used to detect PI3K/AKT pathway-related proteins and EMT markers. The PI3K activator 740Y-P was used for rescue experiments. Results Que inhibited the viability and proliferation of HNSCC cells while inducing apoptosis. Que suppressed the migratory and invasive capacities of the cells, and attenuated EMT-related changes and PI3K/AKT pathway activation. The addition of 740Y-P partially reversed the effects of Que, indicating that the inhibitory effects of Que may be realized through regulating the PI3K/AKT pathway. Conclusion These findings suggest that Que suppressed EMT-related changes in HNSCC cells at least partly through modulating the PI3K/AKT pathway. This study provides in vitro evidence supporting the potential regulatory role of Que in HNSCC cells. However, this study is limited by its in vitro design, and further in vivo and clinical validation is required.