P53途径在辛伐他汀诱导K562细胞凋亡中的作用

Role of P53 pathway in simvastatin-induced apoptosis of K562 cells in vitro

目的探讨辛伐他汀处理后的P53通路和细胞周期的分子水平变化,以说明P53途径在辛伐他汀抑制K562细胞增殖和诱导细胞凋亡中的作用。方法体外培养和用辛伐他汀处理K562细胞,用流式细胞仪检测辛伐他汀作用后的细胞周期和凋亡率的变化,用RT-PCR检测P53通路和细胞周期相关基因的变化。采用免疫组化LDP法检测P21蛋白变化的水平。结果辛伐他汀能使K562细胞停滞在G0/G1期,明显诱导K562细胞凋亡,大多数P53通路基因和细胞周期相关基因出现差异表达。P21蛋白随药物作用时间的延长,表达上调。结论P53通路可能在辛伐他汀诱导的K562细胞增殖抑制和凋亡发生的过程中起重要作用。

Objective To investigate the changes of P53 pathway and cell cycle in K562 cells treated with simvastatin in molecular levels and illustrate the antiproliferative and apoptosis-induced role of P53 pathway in K562 cells when exposed to simvastatin. Methods K562 cells were cultured and treated with simvastatin in vitro. The apoptosis rate and cell cycle of K562 cells were measured by FCM. The transcriptional level changes of most molecules in P53 pathway and cell cycle were detected by RT-PCR. The changes of P21 protein was measured by immunohistochemistry LDP method. Results G0/G1 arrest in K562 cells and significant apoptosis of K562 cells were induced by simvastatin. Most genes in P53 pathway and genes related to cell cycle after exposed to simvastatin were expressed differentially in K562 cells. The P21 protein was up-regulated with the prolongation of simvastatin treatment time. Conclusion P53 pathway probably plays important roles in antiproliferation and apoptosis of K562 cells induced by simvastatin.