辛伐他汀通过氧化应激诱导K562细胞凋亡

Simvastatin induces K562 cell apoptosis by oxidative stress

目的：观察辛伐他汀对K562细胞凋亡的影响，探讨辛伐他汀诱导K562细胞凋亡的分子机制。方法：不同浓度辛伐他汀处理K562细胞，AnnexinV—FITC／PI双染法检测辛伐他汀对K562细胞凋亡的影响。辛伐他汀处理K562细胞48h，流式细胞仪检测活性氧（Reactive oxygen species，ROS）浓度，免疫组织化学法测定突变P53蛋白表达。RT—PCR测定c-junmRNA表达。结果：AnnexinV—FITC／PI双染法检测结果显示，5、10、20μmol／L辛伐他汀作用K562细胞48～72h能诱导其凋亡。辛伐他汀作用K562细胞后，与对照组比较，处理组细胞内ROS明显升高。辛伐他汀处理．K562细胞后突变P53蛋白表达明显下调，c—jun mRNA表达上调。结论：辛伐他汀改变K562细胞内氧化还原状态，细胞氧化应激，下调突变P53蛋白表达，上调c-jun表达诱导K562细胞凋亡。

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 Annexin V -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 20μmol/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.