辛伐他汀对人非小细胞肺癌A549细胞凋亡及caspase-9、caspase-3活性的影响

EFFCT OF SIMVASTATIN ON HUMAN NON-SMALL CELL LUNG CANCER A549 CELL APOPTOSIS AND CASPASE-3 AND CASPASE-9 ACTIVITY

目的:观察辛伐他汀对非小细胞肺癌(NSCLC)细胞凋亡的影响并探讨其机制。方法:辛伐他汀10,20,30μmol/L作用于NSCLC的A549细胞48,72h后,Hoechst 33 258荧光染色法观察细胞形态学改变,流式细胞仪Annexin V-FITC/PI双染法检测细胞凋亡,分光光度法检测caspase-3、caspase-9活性。结果:不同浓度辛伐他汀作用于A549细胞48,72h后,细胞出现典型的凋亡表现,凋亡率明显增高,呈浓度依赖性,且辛伐他汀10,20μmol/L作用72h后,诱导细胞凋亡的作用更显著。同时,辛伐他汀呈浓度依赖性地增强caspase-3、caspase-9活性;其增强caspase-9活性的作用在72h更显著。结论:辛伐他汀能诱导A549细胞凋亡,该作用与其上调caspase-9、caspase-3活性有关。

Objective： To evaluate the effect of simvastatin on the apoptosis of human non-small cell lung cancer （NSCLC） as well as the underlying molecular mechanisms. Methods： NSCLC A549 cell apoptosis was determined using Hoechst 33258 staining and flow cytometry Annexin V-FITC/PI double staining after 48 h or 72 h of the treatment with different concentrations of simvastatin （10,20 and 30μmol/L）. The activity of caspase-3 and caspase-9 was measured by spectrophotometry. Results ： After 48 h or 72 h of the treatment with different concentrations of simvastatin （10,20 and 30μmol/L）,A549 cells showed typical apoptosis performance and apoptosis was significantly increased in a concentration-dependent manner. Mo-reover, after 72 h of the treatment with simvastatin （10 and 20μmol/L）,the apoptosis rate was higher than the 48 h groups. More importantly, simvastatin significantly enhanced caspase-3 and caspase-9 activi-ty in concentration-dependent manner. In addition, after 72 h of the treatment with simvastatin （10,20 and 30 μmol/L）,the caspase-9 activity was higher than the 48 h groups. Conclusion ： These results demon-strate that simvastatin can induce apoptosis of A549 cells and its mechanism is closely related to increased activity of caspase-9 and caspase-3.