title: Resveratrol decreases FoXO protein expression through PI3K-Akt-dependent pathway inhibition in H₂O₂-treated synoviocytes.
abstract: 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.
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, Hefei, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, Hefei, P.R. China.
authors.forename: Gaoyuan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei, P.R. China.
authors.forename: Junqiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei, P.R. China. cxyayd@163.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D000070918:Synoviocytes / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D051858:Forkhead Transcription Factors; D013267:Stilbenes; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol