Glycogen synthase kinase-3? (GSK-3?) involved in the inhibitory effect on proliferation of lung carcinoma cells in vitro / 重庆医科大学学报

ABSTRACT

Objective:To explore the effect of Glycogen synthase kinase-3?(GSK-3?)on cell proliferation in human lung adenocarcinoma cell line A549 and its potential mechanisms.Methods:MTT assay was employed to evaluate the effects of trichostatin A(TSA)and pretreatment with SB216763(a specific inhibitor of GSK-3?)on the proliferation of A549 cells.Western Blot was employed to analyze the protein levels of GSK-3?and phosphorylated GSK-3?(pGSK-3?).Cell life cycle was examined by flow cytometry analysis.The immunocytochemical method was employed to analyze the protein levels of p27.Results:TSA could inhibit the proliferation of A549 cells in a dose-dependent manner and the cell cycle was arrested in G0/G1 phase in A549 cells treated with TSA.While pre-treatment of A549 cells with SB216763 attenuated TSA induced growth inhibiting and cell cycle arrest.TSA did not alter the levels of GSK-3?but decreased pGSK-3?expression and up-regulated p27 expression.As expected,SB216763 increased the levels of pGSK-3?,consistent with inhibition of GSK-3?activity.Inhibition of GSK-3?activity down regulated p27 protein level.Conclusion:GSK-3?was involved in the inhibition of effect induced by TSA on lung carcinoma cells proliferation process.GSK-3?may exert this effect by stabilization of p27 which may be one of the downstream molecules.