THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYOESTRADIOL INHIBITS ANGIOGENESIS AND SUPPRESSES TUMOR-GROWTH
THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYOESTRADIOL INHIBITS ANGIOGENESIS AND SUPPRESSES TUMOR-GROWTH
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DOI：
10.1038/368237a0
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发表时间：
1994-03-17
期刊：
影响因子：
64.8
通讯作者：
SCHWEIGERER, L
中科院分区：
文献类型：
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作者：
FOTSIS, T;ZHANG, YM;SCHWEIGERER, L
新血管的形成（血管生成）对于肿瘤的生长至关重要（1-3），并且是糖尿病视网膜病变、关节炎、血管瘤和银屑病等各种血管生成疾病的主要特征（4）。对控制病理性血管生成的潜在治疗益处的认识导致了对血管生成抑制剂的研究。在这里，我们报告，2-甲氧基雌二醇，以前未知的功能的内源性雌激素代谢产物，是一种有效的抑制剂的内皮细胞增殖和迁移，以及在体外血管生成。此外，当小鼠口服给药时，它强烈抑制实体瘤的新血管形成并抑制其生长。与皮质激素结构的血管抑制类固醇不同（5），它不需要肝素或硫酸化环糊精的共同给药来发挥活性。因此，2-甲氧基雌二醇是第一个本身具有高抗血管生成活性的类固醇。我们的研究结果表明，这种化合物可能具有治疗癌症和其他血管生成疾病的潜力。
THE formation of new blood vessels (angiogenesis) is critical for the growth of tumours(1-3) and is; a dominant feature in various angiogenic diseases such as diabetic retinopathy, arthritis, haemangiomas and psoriasis(4). Recognition of the potential therapeutic benefits of controlling pathological angiogenesis has led to a search for angiogenesis inhibitors. Here we report that 2-methoxyoestradiol, an endogenous oestrogen metabolite of previously unknown function, is a potent inhibitor of endothelial cell proliferation and migration as well as angiogenesis in vitro. Moreover, when administered orally in mice, it strongly inhibits the neovascularization of solid tumours and suppresses their growth. Unlike the angiostatic steroids of corticoid structure(5), it does not require the co-administration of heparin or sulphated cyclodextrins for activity. Thus, 2-methoxyoestradiol is the first steroid to have high antiangiogenic activity by itself. Our results suggest that this compound may have therapeutic potential in cancer and other angiogenic diseases.