Mechanism Research Of Resveratrol Inhibiting Migration And Invasion By Up-regulating TET1 Expression In DU145 Prostate Cancer Cell Line

Objective:Recently,many studies have shown that Resveratrol(Res)could inhibit the migration and invasion of prostate cancer(PCa).This study was designed to investigate the effect of Res on genomic DNA methylation levels,TET1 expression and the ability of migrate and invade in DU 145 cells.Methods:The inhibitory effect of Res on the growth of DU145 cells was verified by cytotoxicity test.The IC50 value was 162.5±1.053μM.The effects of Res on 5mC,5hmC and TET1 levels and on cell migration and invasion were examined.The expression levels of TET1,TIMP2,TIMP3,MMP2 and MMP9 were examined by Western blotting.Subsequently,TET1 was silenced by using lentiviral shRNA to examine the effect of TET1 on Res inhibiting migration and invasion of DU 145 cells.Results:The results showed thatRes could up-regulate the expression of 5hmC and TET1 and down-regulate the expression of 5mC.Res also could inhibit the migration and invasion of PCa,promote demethylation of TIMP2 and TIMP3 promoters,up-regulate expression of them,and inhibit the expression of MMP2 and MMP9.Under the treatment of Res,the expression of silencing TET1 indicated that Res could exert its effect of up-regulating TIMP2,TIMP3 and inhibiting PCa migration and metastasis through TET1.Conclusions:The current findings suggest that Res could inhibit PCa migration and invasion via the TET1/TIMP2/TIMP3 pathway,which migth serve as a target for the treatment of PCa.