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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

5-Aminoimidazole-4-Carboxamide-1-β-D-Ribofuranoside (AICAR) 对三阴性乳腺癌 (TNBC) 细胞的抗癌作用：线粒体调节作为潜在机制

卷 22, 期 3, 2022

发表于: 17 March, 2022

页: [245 - 256] 页: 12

弟呕挨: 10.2174/1568009622666220207101212

价格: $65

摘要

背景：三阴性乳腺癌 (TNBC) 以 Warburg 效应和线粒体缺陷而闻名。 AMP 依赖性激酶 (AMPK) 激活参与线粒体生物发生的下游转录因子 PGC-1α、PGC-1β 或 FOXO1。 5-氨基咪唑-4-甲酰胺核苷 (AICAR) 是单磷酸腺苷的类似物，是 AMPK 的直接激活剂。 目的：在本研究中，我们试图了解 AICAR 对 TNBC 细胞 MDA-MB-231 的影响，以及线粒体生物发生的潜在变化（如果有的话）。 方法：我们研究了 AICAR 诱导的细胞活力、细胞凋亡、迁移潜力的变化以及阿霉素敏感性的变化。 结果：响应于用 750 μM AICAR 处理 MDA-MB-231 乳腺癌细胞 72 小时，然后在没有 AICAR 的新鲜培养基中处理 48 小时，我们通过 MTT 测定观察到活力下降，细胞数量减少随着细胞凋亡的出现，ELISA 增加细胞死亡，条件培养基中的乳酸减少，并且通过划痕和 transwell 迁移测定减少迁移。癌症表型的这些变化伴随着线粒体生物合成的增加，如线粒体 DNA 与核 DNA 比率的增加、乳酸浓度的降低、MitoTracker 绿色和红色染色的增加以及转录因子 PGC- 的表达增加所观察到的。 1α、NRF-1、NRF-2 和 TFAM，有助于线粒体生物发生。通过 MTT 试验评估，用 AICAR 预处理细胞 72 小时，然后用 1 μM 阿霉素处理 48 小时显示对阿霉素的敏感性增加。结论：我们的结果表明，AICAR 对 TNBC 细胞发挥有益作用，可能是通过关闭 Warburg 效应和通过线粒体调节开启抗 Warburg 效应。

关键词: AICAR，细胞凋亡，迁移，活力，化学敏感性，线粒体调节。

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图形摘要

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