组蛋白去乙酰化酶抑制剂Trichostatin-A诱导人乳腺癌MCF-7细胞凋亡的机制 |
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引用本文: | 李琦,王理伟,魏玮,周翡,罗金红,于顺江.组蛋白去乙酰化酶抑制剂Trichostatin-A诱导人乳腺癌MCF-7细胞凋亡的机制[J].中华实验外科杂志,2008,25(4). |
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作者姓名: | 李琦 王理伟 魏玮 周翡 罗金红 于顺江 |
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作者单位: | 1. 同济大学附属东方医院肿瘤医学部,上海,200120 2. 北京世纪坛医院肿瘤中心放疗科 |
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基金项目: | 上海市浦东新区优秀青年医学人才培养计划,同济大学校科研和校改项目 |
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摘 要: | 目的 探讨组蛋白去乙酰化酶抑制剂Trichostatin-A(TSA)诱导肿瘤细胞凋亡的机制.方法 显微镜下观察TSA作用24、48 h后,小鼠NIH3T3成纤维细胞、人乳腺癌MCF-7细胞的形态学变化,采用流式细胞学方法(FCM)检测细胞凋亡情况.利用Western blot方法检测细胞周期相关蛋白Rb蛋白和凋亡相关蛋白多聚ADP核糖聚合酶(PARP)降解片段的表达.结果 TSA作用后的NIH3T3细胞,生长变得缓慢,但细胞尚保持生长的活性.MCF-7细胞24、48 h的凋亡率分别为(36.4±1.5)%、(67.0±2.8)%,以48 h最明显.TSA作用24、48、72 h后,两种细胞均出现不同程度的磷酸化Rb蛋白水平下降,MCF-7细胞中PARP发生明显的降解,48 h后降解明显,72 h达到最大程度.结论 TSA可诱导MCF-7细胞凋亡,其机制可能通过改变肿瘤细胞校染色质的空间结构,以及阻滞细胞周期实现的.
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关 键 词: | 乳腺肿瘤 脱噬作用 组蛋白 去乙酰化酶 |
Mechanisms of TSA-Induced apoptosis of MCF-7 breast cancer cells |
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Abstract: | Objective To investigate the mechanisms of apoptosis by the drug Trichostatin-A (TSA)treatment in MCF-7 breast cancer cell line.Methods The morphological change of cells was observed by microscope after NIH 313,MCF-7 cells treated with TSA for 24,48 h.Flow cytometry was used to detect the apoptceis of the cells.The expression of poly ADP-ribose polymerase PARP was detected by Western blot.Results The growth of the NIH 3T3 cells become very slow after treatment with TSA,but these cells still survived.Meanwhile,the apoptotic rate of MCF-7 cells was(36.4±1.5)% and(67.0±2.8)% after treatment with TSA for 24 and 48 h,more obviously for 48 h(P<0.01).The expression of phosphorylated Rb protein was decreaged in the NIH3T3 and MCF-7 cells.Simultaneously,PARP degradation was observed in MCF-7 cells,more obvious at 48 h,and reached the peak at 72 h.Conclusion TSA can induce the apoptasis of tumor cell MCF-7,which may be related to the change in chromatin conformation and blockade of cell cycle. |
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Keywords: | Breast neoplasms Apoptosis Histone Deacetylase |
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