异乌药内酯对人乳腺癌MCF-7细胞的生长抑制作用及其机制研究
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摘要
目的研究异乌药内酯对人乳腺癌MCF-7细胞生长的抑制作用及其作用机制。方法体外培养MCF-7细胞,分为对照组及不同浓度异乌药内酯处理组。采用MTT实验检测异乌药内酯对MCF-7细胞增殖的影响;采用流式细胞术和TUNEL染色法检测异乌药内酯对MCF-7细胞周期、线粒体膜电位及细胞凋亡的影响;采用Western blotting法检测与细胞凋亡密切相关的蛋白表达情况。结果异乌药内酯以时间和剂量依赖性抑制MCF-7细胞增殖、促进细胞凋亡;能够将MCF-7细胞周期阻滞在G2/M期,诱导线粒体膜电位去极化;上调cleaved Caspase-3和促凋亡蛋白Bax表达,抑制抗凋亡蛋白Bcl-2表达,诱导MCF-7细胞的凋亡。结论异乌药内酯对MCF-7细胞的增殖抑制作用呈剂量和时间依赖性,其作用机制可能是通过线粒体途径诱导细胞凋亡。
Objective To study the effects and the mechanism of isolinderalactone on inhibiting the growth of human breast cancer MCF-7 cells. Methods Human breast cancer MCF-7 cells were cultured in vitro and treated respectively with indicated concentrations of isolinderalactone by cell culture technique. The proliferation rate was detected by MTT method; Flow cytometry and TUNEL assay were used to observe the effects of isolinderalactone on cell cycle, mitochondrial membrane potential and apoptosis in MCF-7 cells; The apoptosis related protein expression levels were determined by Western blotting. Results Isolinderalactone significantly inhibited the proliferation of MCF-7 cells by inducing cell apoptosis in a time and concentration dependent manner and induced cell cycle arrest at G2/M phases. The mitochondrial membrane potential was depolarized; And isolinderalactone up-regulated the expressions of apoptosis related proteins Bax and cleaved Caspase-3 and down-regulated the expressions of apoptosis related proteins Bcl-2. Conclusion Isolinderalactone shows obvious anti-cancer activities by inducing cell apoptosis. The mechanism of inducing apoptosis may be associated with the reduction of mitochondrial membrane potential and activation of caspase pathway.
Objective To study the effects and the mechanism of isolinderalactone on inhibiting the growth of human breast cancer MCF-7 cells. Methods Human breast cancer MCF-7 cells were cultured in vitro and treated respectively with indicated concentrations of isolinderalactone by cell culture technique. The proliferation rate was detected by MTT method; Flow cytometry and TUNEL assay were used to observe the effects of isolinderalactone on cell cycle, mitochondrial membrane potential and apoptosis in MCF-7 cells; The apoptosis related protein expression levels were determined by Western blotting. Results Isolinderalactone significantly inhibited the proliferation of MCF-7 cells by inducing cell apoptosis in a time and concentration dependent manner and induced cell cycle arrest at G2/M phases. The mitochondrial membrane potential was depolarized; And isolinderalactone up-regulated the expressions of apoptosis related proteins Bax and cleaved Caspase-3 and down-regulated the expressions of apoptosis related proteins Bcl-2. Conclusion Isolinderalactone shows obvious anti-cancer activities by inducing cell apoptosis. The mechanism of inducing apoptosis may be associated with the reduction of mitochondrial membrane potential and activation of caspase pathway.
引文
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[2]Clarke R,Leonessa F,Trock B.Multidrug resistance/P-glycoprotein and breast cancer:Review and meta-analysis[J].Semin Oncol,2005,32(S7):9-15.
[3]Scully O J,Bay B H,Yip G,et al.Breast cancer metastasis[J].Cancer Genom Proteom 2012,9(5):311-320.
[4]Hsiao W L W,Liu L.The role of traditional Chinese herbal medicines in cancer therapy-from TCM theory to mechanistic insights[J].Planta Med,2010,76(11):1118-1131.
[5]谷丽华,吴纲,张紫佳,等.应用薄层色谱-生物自显影技术评价乌药等三种中药的抗氧化活性[J].药学学报,2006,41(10):956-962.
[6]刘卫东,温中京,郭伟娣,等.乌药提取物抗疲劳作用的实验研究[J].浙江中医杂志,2006,41(7):428-429.
[7]Chuang H C,Li Y W,Yuen M W,et al.Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2and up regulation of NM23-H1 expression in human lung cancer A549 cells[J].Oncol Lett,2018,15(4):4690-4696.
[8]Ji Y H,Jung H P,Min J K.Isolinderalactone regulates the BCL-2/caspase-3/PARP pathway and suppresses tumor growth in a human glioblastoma multiforme xenograft mouse model[J].Cancer Lett,2018,443(11):25-33.
[9]马丹丹,刘坤,齐晓伟.2018年全球癌症统计:乳腺癌发病和死亡人数统计[J].中华乳腺病杂志:电子版,2018,12(6):375.
[10]宋轶鹏,姜翠芳.乳腺癌治疗策略的转变[J].现代医药卫生,2006,22(12):1827.
[11]Edinger A L,Thompson C B.Death by design:Apoptosis,necrosis and autophagy[J].Curr Opin Cell Biol,2004,16(6):663-669.