咖啡因对缺氧条件下人类胶质母细胞瘤细胞中低氧诱导因子/血管内皮生长因子通路的影响
Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia.
作者信息
Maugeri Grazia, D'Amico Agata G, Rasà Daniela M, Saccone Salvatore, Federico Concetta, Magro Gaetano, Cavallaro Sebastiano, D'Agata Velia
机构信息
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Department of Human Science and Promotion of Quality of Life, the San Raffaele Open University of Rome, Rome, Italy.
出版信息
Anticancer Agents Med Chem. 2018;18(10):1432-1439. doi: 10.2174/1871520618666180209151750.
BACKGROUND
Caffeine represents the most used psychoactive drug in the world acting through different mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme (GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors (HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium growth factor (VEGF), a key player in angiogenesis and cell migration.
METHODS
In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades.
RESULTS
Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and MAPK/ERK signaling pathways both implied in HIFs regulation.
CONCLUSION
The present data give new insight into antitumor activity of caffeine during GBM progression.
背景
咖啡因是世界上使用最广泛的精神活性药物，通过不同的作用机制作用于多个分子靶点。它在多形性胶质母细胞瘤（GBM）中发挥抗癌作用。这种肿瘤的特征是广泛的缺氧灶，可触发缺氧诱导因子（HIFs）的表达。在这些因子中，HIF-1α在诱导血管内皮生长因子（VEGF）中起关键作用，VEGF是血管生成和细胞迁移中的关键因子。
方法
在这项研究中，我们研究了咖啡因是否通过调节缺氧事件来对抗GBM的进展。此外，我们分析了磷酸肌醇三激酶（PI3K）/Akt和哺乳动物丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号级联的激活情况。
结果
我们的结果表明，这种精神兴奋药物显著降低了暴露于缺氧环境的GBM细胞中HIF-1α和VEGF的表达。这种作用是通过抑制PI3K/Akt和MAPK/ERK信号通路介导的，这两条信号通路都参与了HIFs的调节。
结论
目前的数据为咖啡因在GBM进展过程中的抗肿瘤活性提供了新的见解。
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