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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

姜黄素通过抑制Zeste Homolog-2（EZH2）增强剂对骨髓增生异常综合症的抗癌作用。

卷 19, 期 9, 2019

页: [729 - 741] 页: 13

弟呕挨: 10.2174/1568009619666190212121735

价格: $65

摘要

背景：zeste homolog-2（EZH2）的增强子，一种调节赖氨酸27（H3K27me3）的组蛋白H3甲基化的组蛋白甲基转移酶，参与了骨髓增生异常综合症（MDS）的发病机理。靶向表观遗传调节剂已被确定为MDS化疗的潜在治疗靶标。姜黄素是一种从姜黄中提取的天然化合物，被发现在各种肿瘤中具有广泛的抗癌活性。 方法：本研究旨在探讨姜黄素在体外和体内对骨髓增生异常综合症（MDS）的抑制作用和作用机理。 结果：我们的结果表明，姜黄素可以显着抑制人MDS衍生细胞系中的细胞增殖，并诱导细胞凋亡和细胞周期停滞。它减少了EZH2，DNA甲基转移酶3A（DNMT3a），ASXL1和下游H3K4me3，H3K27me3和HOXA9的表达，并抑制了EZH2和H3K27me3的核易位。姜黄素在异种移植小鼠模型中也显示出抗癌作用，并且体内的EZH2，H3K4me3和H3K27me3减少。 EZH2敲低可以降低H3K27me3水平，并在体外诱导姜黄素抗性，但在体内减弱白血病的转化。 结论：这些发现为姜黄素作为MDS的治疗剂提供了潜在的分子机制。

关键词: 骨髓增生异常综合症，姜黄素，EZH2，H3K27me3，HOXA9，骨髓增生异常综合症（MDS）。

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