摘要
目的考察洛伐他汀抗A549肺癌细胞增殖的作用,并对其作用机制进行初步的探讨。方法复苏并培养A549肺癌细胞株,给于洛伐他汀(0,20,40,80μmol/L)进行24 h干预或者给于洛伐他汀(40μmol/L)作用12,24,48 h。采用MTT法检测洛伐他汀对A549细胞的增殖抑制作用;用流式细胞术检测洛伐他汀对A549细胞凋亡的影响;用Western blot检测A549细胞增殖相关蛋白p-mTOR、p-p70S6k、凋亡相关蛋白Caspase-3、Caspase-9、PARP以及TAZ表达的影响。设置阴性对照组、TAZ过表达组、洛伐他汀(40μmol/L)组、TAZ过表达+洛伐他汀(40μmol/L)组,预先采用质粒过表达TAZ蛋白,转染48 h加入洛伐他汀(40μmol/L)继续干预24 h,考察TAZ在洛伐他汀抗A549细胞增殖中的作用。结果MTT法检测结果显示,洛伐他汀(0,20,40,80μmol/L)作用于A549细胞后,A549的细胞生存率随浓度和时间依赖性地降低(P<0.05)。Western blot结果显示,洛伐他汀(0,20,40,80μmol/L)浓度依赖性地抑制了p-AKT、p-mTOR和p-p70S6k的表达(P<0.05)。流式结果显示,洛伐他汀(0,20,40,80μmol/L)浓度依赖性地诱导A549细胞发生凋亡(P<0.05)。Western blot结果显示,洛伐他汀(0,20,40,80μmol/L)作用24 h后,cleaved Caspase-3、cleaved Caspase-9、cleaved PARP的表达浓度依赖性地升高(P<0.05),TAZ的表达浓度依赖性地降低(P<0.05)。过表达TAZ可明显减弱洛伐他汀对A549细胞的增殖抑制作用,差异具有统计学意义(P<0.05)。结论洛伐他汀通过抑制TAZ的表达抗A549肺癌细胞增殖。
Objective To investigate the effect of lovastatin on the proliferation of A549 lung cancer cells and explore its mechanism.Methods Lung cancer cell line A549 cells were resuscitated and cultured,and then treated with lovastatin(0,20,40,80μmol/L)for 24 h,or 40μmol/L lovastatin for 12,24,48 h.The inhibitory effect of lovastatin on A549 cells was detected by MTT assay.The effect of lovastatin on apoptosis of A549 cells was detected by flow cytometry.The effects of lovastatin on the expression levels of p-mTOR,p-p70S6k,Caspase-3,Caspase-9,PARP and TAZ in A549 cells were detected by Western blot.A549 cells were transfected with overexpressed TAZ plasmid for 48 h and then treated with lovastatin(40μmol/L)for 48 h,and the proliferation of A549 cells was detected.Results MTT result showed that the survival rate of A549 cells was decreased in a dosage-and time-dependent manner after treatment with lovastatin(P<0.05).Western blot showed that lovastatin(0,20,40,80μmol/L)inhibited the expression of p-AKT,p-mTOR and p-P70S6k in a dosage-dependent manner(P<0.05).Flow cytometry result showed that lovastatin(0,20,40,80μmol/L)induced the apoptosis of A549 cells in a dosage-dependent way(P<0.05).Western blot result showed that lovastatin(0,20,40,80μmol/L)increased the expression levels of cleaved Caspase-3,Caspase-9 and PARP in a dosage-dependent manner(P<0.05).Western blot showed that lovastatin(0,20,40,80μmol/L)inhibited the expression of TAZ in a dosage-dependent manner(P<0.05).Overexpression of TAZ significantly reduced the inhibitory effect of lovastatin on A549 cells(P<0.05).Conclusion Lovastatin can inhibit the proliferation of A549 lung cancer cells by inhibiting TAZ expression.
作者
胡芃
郑艺
赵于飞
吴爱林
毛云飞
常娜
HU Peng;ZHENG Yi;ZHAO Yufei;WU Ailin;MAO Yunfei;CHANG Na(Department of Radiation Oncology,West District,First Affiliated Hospital of University of Science and Technology of China,Hefei 230001,China;Department of Radiation Oncology,Anhui Provincial Cancer Hospital)
出处
《山西医科大学学报》
CAS
2021年第4期391-397,共7页
Journal of Shanxi Medical University
基金
国家自然科学基金资助项目(11805198)。
