Inhibition of tumor angiogenesis by cannabinoids
Inhibition of tumor angiogenesis by cannabinoids
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DOI：
10.1096/fj.02-0795fje
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发表时间：
2003-01-01
期刊：
影响因子：
4.8
通讯作者：
Guzmán, M
中科院分区：
文献类型：
--
作者：
Blázquez, C;Casanova, ML;Guzmán, M
大麻素是大麻及其衍生物的活性成分，可诱导啮齿动物的肿瘤消退(8)。然而，大麻素在体内抗肿瘤作用的机制尚不清楚。通过免疫组织化学分析和血管通透性测定，我们发现局部给药一种非精神活性大麻素可以抑制恶性胶质瘤的血管生成。体外和体内实验表明，大麻素的作用可能涉及至少两种机制：直接抑制血管内皮细胞的迁移和存活，降低肿瘤中促血管生成因子（血管内皮生长因子和血管生成素-2）和基质金属蛋白酶-2的表达。抑制肿瘤血管生成可能为设计基于大麻素的抗肿瘤疗法提供新的策略。
Cannabinoids, the active components of marijuana and their derivatives, induce tumor regression in rodents (8). However, the mechanism of cannabinoid antitumoral action in vivo is as yet unknown. Here we show that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays. In vitro and in vivo experiments show that at least two mechanisms may be involved in this cannabinoid action: the direct inhibition of vascular endothelial cell migration and survival as well as the decrease of the expression of proangiogenic factors (vascular endothelial growth factor and angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor angiogenesis may allow new strategies for the design of cannabinoid-based antitumoral therapies.