Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.

摘要: Purpose Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)-induced cell and the underlying mechanisms remain unclear. Methods Effects fisetin EGF-induced viability were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) vitro assays. Reverse transcription-PCR (RT-PCR) immunoblotting performed evaluate matrix metallopeptidase-9 (MMP-9) expression activation specificity protein-1 (Sp1) protein kinase B (AKT) ARPE-19 cells treated EGF or without fisetin. Luciferase chromatin immunoprecipitation (ChIP) assays examine Sp1 transcription activity MMP-9 binding activity. Results did not affect significantly inhibited capacity Furthermore, exerted an antimigratory effect suppressed mRNA expression. Treatment induced phosphorylation AKT Sp1. combined LY294002 (an inhibitor AKT) prevented involved downregulation ChIP suggested remarkably decreased EGF-mediated from directly promoter Conclusions via modulation AKT/Sp1-dependent transcriptional Therefore, may be potential agent treatment migratory PVR diseases.