辛伐他丁对淋巴瘤CA46细胞凋亡的影响及机制

Simvastatin induces apoptosis of lymphoma CA46 cells and its underlying mechanisms

目的:研究内源性胆固醇合成限速酶(HMG-CoA)还原酶抑制剂辛伐他汀对淋巴瘤细胞凋亡的影响及分子机制。方法:辛伐他汀对淋巴瘤CA46细胞株进行干预,MTT法评价二者对癌细胞增殖的影响;流式细胞计量术检测细胞凋亡;免疫印迹法检测凋亡相关蛋白多聚ADP核糖多聚糖蛋白(PARP)、半胱氨酸蛋白酶-3(Caspase-3)、凋亡相关基因Bax、Bcl-2表达情况。结果:辛伐他汀干预可显著抑制CA46细胞MTT活性,辛伐他汀作用还可促进CA46细胞凋亡的启动,且均呈剂量-效应关系;辛伐他汀干预还可引发CA46肿瘤细胞Caspase-3活性水平升高,PARP裂解失活,促凋亡蛋白Caspase-3、Bax高表达,抗凋亡蛋白Bcl-2表达降低,且均呈现时间-效应关系。结论:辛伐他汀对淋巴瘤CA46细胞具有增殖抑制和促凋亡效应,其机制可能与caspase家族介导的蛋白酶级联反应、PARP裂解失活以及Bcl-2家族介导的细胞色素C途径有关。

Objective. To investigate the anti proliferative effects of simvastatin on lymphoma cells and its underlying mechanisms. Methods：CA46 cells were interfered by Simvastatin, MTT assay was used to evaluate the anti-proliferative effects, Flow cytometry assay was used to detect apoptosis; Western blot analysis was used to detect the protein expression of PAP, P, Caspase-3 and apoptosis-related molecules Bax.Bcl-2. Results= The MTT and FCM data shows that Simvastatin inhibited activity of CA46 cell, and caused apoptosis of CA46 cell in a dose-dependent manner. The expression level of Caspase-3 and cleavage of PARP was significantly increased when treated with simvastatin. The expression of Bax was also in-