Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent
Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent
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DOI：
10.1016/s0006-2952(98)00046-x
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发表时间：
1998-06-01
影响因子：
5.8
通讯作者：
Figg, WD
中科院分区：
文献类型：
--
作者：
Bauer, KS;Dixon, SC;Figg, WD
沙利度胺已被证明是兔角膜微囊模型中的血管生成抑制剂;然而，它未能在其他模型中证明这种活性。这些结果表明，沙利度胺的抗血管生成作用可能仅在化合物代谢活化后观察到。这种激活过程可能是物种特异性的，类似于与沙利度胺相关的致畸特性。使用大鼠主动脉模型和人主动脉内皮细胞，我们共孵育沙利度胺存在的人，兔，或大鼠肝微粒体。这些实验表明，沙利度胺抑制大鼠腹主动脉微血管形成和减缓人或兔微粒体的存在下，但不存在大鼠微粒体的人主动脉内皮细胞增殖。在不存在微粒体的情况下，沙利度胺对微血管形成或细胞增殖均无影响，因此证明沙利度胺的代谢产物负责其抗血管生成作用，并且该代谢产物可在人和兔中形成，但不在啮齿动物中形成。(C)1998年爱思唯尔科学公司
Thalidomide has been shown to be an inhibitor of angiogenesis in a rabbit cornea micropocket model; however, it has failed to demonstrate this activity in other models. These results suggest that the anti-angiogenic effects of thalidomide may only be observed following metabolic activation of the compound. This activation process may be species specific, similar to the teratogenic properties associated with thalidomide. Using a rat aorta model and human aortic endothelial cells, we co-incubated thalidomide in the presence of either human, rabbit, or rat liver microsomes. These experiments demonstrated that thalidomide inhibited microvessel formation from rat aortas and slowed human aortic endothelial cell proliferation in the presence of human or rabbit microsomes, but not in the presence of rat microsomes. In the absence of microsomes, thalidomide had no effect on either microvessel formation or cell proliferation, thus demonstrating that a metabolite of thalidomide is responsible for its anti-angiogenic effects and that this metabolite can be formed in both humans and rabbits, but not in rodents. (C) 1998 Elsevier Science Inc.