Resveratrol decreases FoXO protein expression through PI3K-Akt-dependent pathway inhibition in H₂O₂-treated synoviocytes.

The aim of this study was to investigate the effects of resveratrol (Res) on hydrogen peroxide (H₂O₂)-treated fibroblast-like synoviocytes (FLSs) in vitro. We studied the phosphoinositide 3-kinase (PI3K)-Akt pathway inhibition-mediated effects of Res on forkhead box O (FoXO) mRNA expression levels. FLS viability was determined by Cell Counting Kit-8 (CCK-8) assay, and FLS apoptosis was measured by terminal deoxyribo nucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. FoXO1, FoXO3 and FoXO4 mRNA expression levels in FLSs were determined by RT-PCR, and p-Akt, Akt, p-FoXO1, FoXO1, p-FoXO3, FoXO3, Bcl-2 and Bax protein expression levels were determined by western blotting. Our results showed that low H₂O₂ concentrations (20 μM) can promote FLS growth and that Res significantly inhibited FLS activity. Moreover, Res significantly increased the number of apoptotic cells and the ratio of Bax/Bcl-2 protein expression in the group treated with Res compared with the group treated with H₂O₂ and LY294002, a PI3K inhibitor. Res also decreased FoXO1, FoXO3 and FoXO4 mRNA expression levels and p-Akt/Akt, p-FoXO1/FoXO1, p-FoXO3/FoXO3 protein expression levels. Taken together, these findings indicate that Res can induce apoptosis in H₂O₂-treated FLSs in part by inhibiting the PI3K-Akt signaling pathway.