P57 inhibits proliferation of U87 glioblastoma cells to reduce toxic damage induced by temozolomide / 中华神经医学杂志

ABSTRACT

Objective To analyze the relation between short-term chemotherapy of temozolomide (TMZ) and inhibition of proliferation of U87 glioblastoma cells,and investigate the role and mechanism of P57 in inhibiting U87 cells proliferation under treatment of TMZ.Methods Protein levels of P57 and proliferating cell nuclear antigen Ki-67 in U87 cells accepted TMZ short-term chemotherapy were detected by Western blotting.Protein levels of P57 in clinical primary or recurrent glioblastomas accepted TMZ short-term chemotherapy were compared by immunohistochemistry and Western blotting.After P57 was knocked down,apoptosis,cell cycle and cell vitality changes of U87 cells treated with TMZ and U87 cells with TMZ withdrawal were studied.Results After short-term chemotherapy of TMZ in U87 cells,the expression level of P57 increased but the expression level of Ki-67 decreased.The protein level of P57 in recurrent glioblastoma was higher than that in primary tumor.After P57 was knocked down in U87 cells treated with TMZ,apoptosis was enhanced and the protein level of cycle dependent kinase 2 (Cdk2) increased,which indicated that the inhibition of proliferation induced by TMZ was weakened,while the apoptosis rate increased (31.00±3.48 vs.12.83±1.40) Furthermore,after TMZ was withdrew,the cell cycle and cell vitality in U87 control cells recovered,but in U87 cells with P57 knocked down,the cell cycle was arrested and the cell vitality was reduced.Conclusion P57 inhibits cell cycle progression or proliferation of U87 cells by up-regulating P57 expression and inhibiting Cdk2 expression to reduce the damage caused by TMZ.