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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

Shikonin衍生的DMAKO-20通过CYP1B1对黑色素瘤的选择性抗肿瘤作用。

卷 21, 期 3, 2021

发表于: 16 November, 2020

页: [223 - 231] 页: 9

弟呕挨: 10.2174/1568009620666201116112937

价格: $65

摘要

背景：CYP1B1被认为是化疗的重要靶标。它催化某些癌细胞系中萘醌肟的生物活化。然而，CYP1B1在黑色素瘤中的表达水平和调节DMAKO-20作为代表性萘醌肟抗皮肤癌活性的功能仍是未知的。目的：探讨CYP1B1在黑素瘤中的表达水平，探讨DMAKO-20抗黑素作用的分子机制。 方法：采用免疫组织化学方法检测CYP1B1在黑色素瘤患者石蜡标本中的表达水平及其在B16 / F10癌细胞中的表达水平。 DMAKO-20抗黑色素瘤活性的分子机制是通过使用细胞毒性，细胞损伤，凋亡和免疫印迹试验进行研究的。 结果：CYP1B1，P450亚型，在黑素瘤组织和培养的B16 / F10细胞中高水平表达，但在正常组织或成纤维细胞中未检测到。在细胞增殖试验中，紫草素肟DMAKO-20对B16 / F10黑色素瘤细胞表现出有效的和选择性的抗增殖作用，并抑制了迁移。在B16 / F10黑色素瘤细胞中已经确定了DMAKO-20抗癌作用的几种机制，包括细胞凋亡，线粒体凋亡Bax蛋白的上调和抗凋亡Bcl-2的下调。这些机制研究的结果表明，DMAKO-20经历了CYP1B1介导的代谢活化，从而激活了黑色素瘤细胞内的抗癌代谢产物。 结论：DMAKO-20通过CYP1B1介导的活化对黑素瘤细胞具有选择性的细胞毒性作用。使用DMAKO-20作为先导化合物，进一步的结构优化可以为治疗恶性皮肤癌提供新的药物实体。

关键词: 皮肤癌，黑色素瘤，紫草素，化学疗法，细胞色素P450，pProdrug。

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