Simvastatin induces K562 cell apoptosis by oxidative stress

Objective: To investigate the effects of simvastatin on K562 cells apoptosis and elucidate its molecular mechanisms. Methods: K562 cells were treated with various concentrations of simvastatin for different time,and then AnnexinⅤ-FITC/PI staining was performed to confirm the apoptosis of K562 cells. Flow cytometry was employed to measure ROS level;mutant P53 protein expression level in K562 cells was measured by immunohistochemistry method. RT-PCR was employed to analyze the mRNA expression levels of c-jun. Results: K562 cells were induced to undergo apoptosis after 5,10 μmol/L and 20 μmol/L simvastatin treatment for 48 h and 72 h. After the treatment of 10 μmol/L and 20 μmol/L simvastatin for 48 h,compared with the control group,ROS level in K562 cells increased obviously. Immunohistochemistry results indicated that simvastatin could inhibit protein expression levels of mutant-type P53. RT-PCR results showed that simvastatin could increase the mRNA expression levels of c-jun significantly. Conclusion: Simvastatin induces K562 cells apoptosis by down-regulating mutant P53 protein and up-regulating c-jun mRNA expression which might be caused by changes of intracellular redox state.