Intervention Of MPST Overexpression On Effects Of Sodium Arsenite On The Cell Cycle Of SH-SY5Y Cells And Underlying Mechanisms

Aim:To investigate the effects of sodium arsenite（NaAsO₂）and the MPST over-expression on the cell cycle and growth,and the underlying mechanisms in the neural cells.Methods:NaAsO₂ and ATM inhibitor KU60019 were used to treat SH-SY5Y neuroblastoma cells for 48h in the blank control（BC）,empty vector control（transfected with empty vector,NC）and MPST overexpression group（MPST-OP）.The cell viability,adherent rate,cell cycle and protein expression of P53,CDC25A,CyclinA and CDK2 were examined with CCK-8,Crystal violet staining,flow cytometry and western blot assay.Results:（1）NaAsO₂(0,5,10,20,50,75,100μmol·L^-1)can decrease the cell viability of the SH-SY5Y cells at different time（24,48,72 h）in the dose and time dependent manners and the half maximal inhibitory concentration（IC50）in SH-SY5Y cells was 50μmol·L^-1 after 48 h;（2）The decrease in the cell viability and adherent rate was reversed significantly in MPST-OP group after treatment with NaAsO₂ for 48 h（p<0.01）;（3）NaAsO₂ treatment significantly increased the proportion of S phase in NC group（p<0.01）,and this effect was inhibited in MPST-OP group（p<0.01）;（4）NaAsO₂ significantly increased P53protein expression in NC group（p<0.01）and down-regulated protein levels of CDC25A,CyclinA and CDK2 in BC and NC groups（p<0.01）,whereas the above changes of protein levels in MPST-OP group were significantly antagonized compared with those of NC group.（p<0.01）;（5）KU60019 significantly down-regulated P53 protein expression and increased protein levels of CDC25A,CyclinA and CDK2 and the proportion of S phase in BC,NC and MPST-OP groups（p<0.05）.Conclusion:NaAsO₂ may inhibit the cell growth by inducing S-phase arrest via ATM signal pathways and over-expression of MPST could reverse the noxious effects caused by NaAsO₂ in SH-SY5Y cells.