Resveratrol inhibits the progression of oral squamouscell carcinoma through Norad/Igf2bp2/Pdk1 pathway and remodeling glucose metabolism reprogramming.

OBJECTIVE: This study investigated resveratrol impact on oral squamous cell carcinoma (OSCC) via the NORAD/IGF2BP2/PDK1 pathway. METHODS: CAL-27, SCC-25, and KB cell lines were used to evaluate cell proliferation, cell cycle arrest, and protein expression. Key molecular markers were assessed using Western blot, RNA interference, and functional assays. RESULTS: Resveratrol inhibited the growth of CAL-27, KB, and SCC-25 cancer cell lines in a dose-dependent manner, with IC50 values of 70, 145, and 125 μg/mL, respectively (P < 0.01). In CAL-27 cells, 50 μg/mL resveratrol induced G2/M arrest (P < 0.05); 100 μg/mL caused S and G2/M phase arrest (P < 0.01). Thirteen proteins changed significantly: cPKCα and Notch4 were upregulated, while p-ERK, p-PDK1, p-Cdc2, p-RB, NORAD, IGF2BP2, CDK2, Cdc2P34, Cyclin E, 14-3-3beta, and XIAP were downregulated. si-NORAD groups showed lower CAL-27 proliferation than control. IGF2BP2 silencing reduced proliferation to 69.13% in HSC3 and 74.01% in CAL-27 (P < 0.001) and decreased invasion to 72.85% and 52.44% (P < 0.001). PDK1 overexpression enhanced the proliferation and migration of hypopharyngeal cancer cells. CONCLUSION: Resveratrol inhibits OSCC proliferation, particularly in CAL-27 cells. It affects NORAD, IGF2BP2, and PDK1 pathways, altering cell cycle protein expression and causing S and G2/M phase arrest.