Abstract: Objective: To investigate the effect resveratrol on glycolysis of oral squamous cell carcinoma (OSCC) by regulating mTOR/PKM2 axis. Methods: OSCC cell lines CAL-27 and SCC-15 were cultured and treated with different concentrations of resveratrol (0 μmol/L, 50 μmol/L, 100 μmol/L, 200 μmol/L, 400 μmol/L, and 800 μmol/L) for 24 h. Cell proliferation was evaluated by MTT assay, and the value of IC₅₀ was calculated. OSCC cells were treated with 250 μmol/L resveratrol or 10 nmol/L rapamycin (mTOR inhibitor) for 24 h, and then the cellular glucose uptake was assessed by 2-NBDG staining. Lactate production in the cell supernatant and the activity of hexokinase and pyruvate kinase in the cells were detected using colorimetric method. The proteins expression of hexokinase-2 (HK2), M2 isoform pyruvate kinase (PKM2), mTOR, and p-mTOR in the cells were analyzed by Western blotting. Results: Resveratrol had an obvious inhibitory effect on the proliferation of CAL-27 and SCC-15 cells in a concentration dependent manner (P＜0.05). Resveratrol intervention significantly inhibited the glucose uptake and decreased the production of lactate in both OSCC cells (P<0.05). It also significantly inhibited the activity of pyruvate kinase and decreased the protein expression of PKM2 in CAL-27 and SCC-15 cells (P<0.05). However, it had no significant effect on the activity of hexokinase and the protein expression of HK-2 (P>0.05). At the same time, resveratrol intervention also significantly decreased the phosphorylation level of mTOR (P<0.05). In addition, rapamycin intervention could also inhibit glucose uptake, decrease the production of lac- tate and the phosphorylation level of mTOR, and down-regulate the protein expression of PKM2 in CAL-27 and SCC-15 cells. Conclusion: Resveratrol inhibits the glycolysis of OSCC cells, and its mechanism might relate to the inhibition of the mTOR/PKM2 axis pathway.

Key words: Resveratrol, Oral squamous cell carcinoma, Glycolysis mTOR/PKM2 axis