Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis

Introduction Resveratrol, a polyphenol extracted from many plant species, has emerged as promising pro-apoptotic agent in various cancer cells. However, the role of resveratrol cell proliferation and apoptosis fibroblast-like synoviocytes rheumatoid arthritis (RA-FLS) is not fully understood. The study was aimed at elucidating RA-FLS underlying molecular mechanism. Material methods Cultured RA-FLSs were subjected to tumour necrosis factor  (TNF-). measured by Cell Counting Kit-8 assay. cycle determined flow cytometry. levels or autophagy cycle-related protein detected immunoblot analysis. Results In our study, we confirmed that reversed TNF- mediated RA-FLS. Meanwhile, blocked cells G2/M stage reduced ratio S phase through upregulation p53 consequently led apoptotic death. Quite interestingly, found TNF--induced autophagy. Inhibition inhibitor Beclin-1 siRNA suppressed survival promoted apoptosis. inducer rapamycin (RAPA) effect on proliferation. Mechanistic studies revealed inhibited activation phosphoinositide 3-kinases/serine-threonine kinase (PI3K/AKT) pathway. PI3K/AKT pathway LY294002 increased expression decreased (cyclin B1), which further block arrest. Conclusions Our preliminary indicated may suppress promote least partly regulation AKT-p53 axis.