摘要
目的探讨辛伐他汀抑制K562细胞增殖并诱导其凋亡的分子机制。方法不同浓度辛伐他汀作用K562细胞后,MTT法检测细胞增殖情况,AnnexinⅤ-FITC/PI双染法检测细胞凋亡情况,RT-PCR测定MAPK1、cyclinD1、E2F1、c-myc mRNA表达。结果辛伐他汀能抑制K562细胞增殖,增殖抑制效应随药物浓度增加和作用时间延长而增大(P<0.05)。与对照组比较,5、10、20μmol/L辛伐他汀作用K562细胞48h和72h后能明显增加细胞凋亡率,差异具有统计学意义(P<0.05),表明辛伐他汀能诱导K562细胞凋亡。10、20μmol/L辛伐他汀处理K562细胞72h后,MAPK1、cyclinD1、E2F1、c-mycmRNA表达水平明显降低。结论辛伐他汀可能通过调节Ras-MAPK途径抑制K562细胞增殖并诱导其凋亡。
Objective To investigate the effects of simvastatin on the cell proliferation and apoptosis of K562 cells and to elucidate its molecular mechanisms. Methods K562 cells were treated with various concentrations of simvastatin for different times, and then MTT assay was employed to evaluate the proliferation of K562 cells. Annexin Ⅴ-FITC/PI staining was performed to confirm the apoptosis of K562 cells. RT-PCR was employed to analyze the mRNA expression levels of MAPK1, cyclin D1, E2F1 and c-myc in K562 cells after simvastatin treatment for 72 h. Results Simvastatin inhibited the proliferation of K562 cells, and the inhibitory rate was increased in a dose- and time-dependent manner. K562 cells were induced to apoptosis after the treatment of simvastatin. Compared to control group, the increased apoptotic rate was observed after K562 cells treated with 5, 10 and 20 μmol/L simvastatin for 48 h and 72 h. RT-PCR results showed that simvastatin downregulated the expressions of MAPK1, cyclin D1, E2F1 and c-myc significantly at mRNA level. Conclusion Simvastatin inhibits the proliferation of K562 cells and induces them to undergo apoptosis, and the underlying mechanism might be related to down-regulation of some molecules in Ras/MAPK pathway.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2009年第3期241-244,共4页
Journal of Third Military Medical University
基金
四川省卫生厅基金(060119)~~
