Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis
Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis
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DOI：
10.1016/s0014-2999(99)00765-7
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发表时间：
1999-12-10
影响因子：
5
通讯作者：
Oikawa, T
中科院分区：
文献类型：
--
作者：
Nakamura, M;Katsuki, Y;Oikawa, T
口服dienogest （17 α -氰甲基-17 β -羟基雌二醇-4,9-二烯-3- 1）对严重免疫缺陷小鼠和实验性子宫内膜异位症大鼠的人类激素依赖性癌症异种移植物有效，但其作用机制尚不清楚。我们评估了地孕激素对血管生成的影响，因为已知这两种对地孕激素敏感的疾病是血管生成依赖的。局部地孕酮处理对胚胎血管生成的抑制呈剂量依赖性，ID50值为6.4 nmol/卵。在小鼠背气囊实验中，连续5天口服dienogest (1 mg kg（-1) day(-1)）可显著抑制S-180小鼠肿瘤细胞诱导的血管生成。体外实验表明，浓度高达10 μ M的dienogest对微血管内皮细胞的纤溶酶原激活物活性增殖或管状结构的形成几乎没有影响。这些结果提示dienogest是一种新型的口服血管生成拮抗剂，其抗血管生成作用可能与我们之前观察到的肿瘤异种移植和子宫内膜异位症的治疗作用有关。(C) 1999 Elsevier Science B.V.版权所有
Orally administered dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-diene-3-one) is efficacious against human hormone-dependent cancer xenografts in severely immunodeficient mice and in rats with experimental endometriosis, but its mechanisms of action remain unclear. We assessed the effect of dienogest on angiogenesis, because these two diseases that are sensitive to dienogest are known to be angiogenesis-dependent. Topical dienogest treatment dose-dependently inhibited embryonic angiogenesis, the ID50 value being 6.4 nmol/egg. Oral administration of dienogest (1 mg kg(-1) day(-1)) for 5 consecutive days significantly suppressed angiogenesis induced by S-180 mouse tumor cells in the mouse dorsal air sac assay. In vitro experiments showed that dienogest at concentrations up to 10 mu M had little or no effect on the proliferation of plasminogen activator activity or formation of tube-like structures by microvascular endothelial cells. These results suggest that dienogest is a new, orally active antagonist of angiogenesis, and that its anti-angiogenic action may be involved in its therapeutic effects on cancer xenografts and endometriosis that we observed previously. (C) 1999 Elsevier Science B.V. All rights reserved.