目的 研究阿托伐他汀对人肺癌HCC827细胞增殖和凋亡的影响并探究其机制。方法 台盼蓝染色计数法检测阿托伐他汀对HCC827细胞的增殖抑制作用;Hoechst 33342和TUNEL法检测细胞凋亡;DCFH-DA荧光探针检测活性氧(ROS)水平;比色法检测丙二醛(MDA)含量变化;Western blot法检测P-H2A.X、Cleaved-caspase 3、Bax和Bcl-2蛋白表达。结果 阿托伐他汀可抑制HCC827细胞生长并诱导细胞凋亡;阿托伐他汀作用后,细胞核形态发生了改变,细胞核染色质浓缩、呈新月状等凋亡特征;随着阿托伐他汀浓度的增加细胞内ROS和MDA含量不断增加;阿托伐他汀可上调细胞中P-H2A.X、Cleaved-caspase 3和Bax蛋白表达,下调Bcl-2蛋白表达,Bax/Bcl-2比值上调。结论 阿托伐他汀抑制HCC827细胞的增殖并诱导细胞凋亡,产生凋亡的机制可能与氧化应激和线粒体介导途径有关。
Abstract
OBJECTIVE To investigate the effect of atorvastatin on proliferation and apoptosis of human lung cancer HCC827 cells and explore its mechanism. METHODS The inhibitory effect of atorvastatin on the proliferation of HCC827 cells was detected by trypan blue staining. Cell morphology was observed under optical microscope. Hoechst 33342 and TUNEL assay were used to detect apoptosis. The level of reactive oxygen species (ROS) was detected by DCFH-DA fluorescent probe. Colorimetric method was used to detect the content of malondialdehyde (MDA). The expression levels of P-H2A.X and apoptosis related proteins cleaved-caspase 3, Bax and Bcl-2 were detected by Western blot. RESULTS Atorvastatin inhibits the growth of HCC827 cells and induces apoptosis. The nuclear morphology of HCC827 cells changed and the nucleus showed apoptotic features such as chromatin condensation, crescent shape and so on after atorvastatin treatment. The levels of ROS and MDA were increased with the increase of atorvastatin concentration compared with the control group. Atorvastatin up-regulated the expression of P-H2A.X, cleaved caspase 3 and Bax protein in HCC827 cells, down-regulated the expression of Bcl-2 protein, and up-regulated the ratio of Bax/Bcl-2. CONCLUSION Atorvastatin inhibits proliferation of HCC827 and induces apoptosis, which may be related to oxidative stress and mitochondrial mediated pathway.
关键词
阿托伐他汀 /
HCC827细胞 /
增殖 /
凋亡 /
氧化应激
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Key words
atorvastatin /
HCC827 cells /
proliferation /
apoptosis /
oxidative stress
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中图分类号：
R965
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参考文献
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脚注
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基金
国家自然基金项目资助(81402414);河北省自然基金面上项目资助(H2015206380)
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