Arsenic trioxide inhibits phosphorylation of P27~(kip1) threonine residue 187 in human hepatic carcinoma cells / 基础医学与临床

ABSTRACT

Objective To investigate the relationship between growth inhibiting effect of arsenic trioxide(As_2O_3) and phosphorylation of P27kip threonine residue 187(P27T187) in human hepatocellular carcinoma(HCC) cell line SMMC-7721.Methods SMMC-7721 were treated for 72 h with 2 ?mol/L As_2O_3.The cell growth inhibition was detected by cell counting and the cell cycle was detected by flow cytometry(FCM).The expression and localization of P27,T187 phosphorylated P27(p-P27T187) were detected by Subcellular Fractionation,Western blot and immunoflurescence.Results As_2O_3 significantly inhibited the proliferation of SMMC-7721 cell and cell cycle was arrested in G2/M.A significant decrease in p-P27T187 expression and a reciprocal increase in P27 expression were found in 2 ?mol/L As_2O_3-treated SMMC-7721 cell.Meanwhile,As_2O_3 decreased the protein levels of Cdk2 and cyclinE.The location of P27 was transferred from cytoplasm to nuclei and the expression of p-P27T187 was decreased in nuclei.Conclusion As_2O_3 inhibits the phosphorylation of P27T187,thereby promoting P27 accumu-lation in SMMC-7721 cell nuclei,inducing cel1 cycle arrest and growth inhibition.