Bauer K S, Dixon S C, Figg W D
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Biochem Pharmacol. 1998 Jun 1;55(11):1827-34. doi: 10.1016/s0006-2952(98)00046-x.
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.
沙利度胺在兔角膜微袋模型中已被证明是一种血管生成抑制剂；然而，它在其他模型中未能显示出这种活性。这些结果表明，沙利度胺的抗血管生成作用可能仅在该化合物代谢活化后才能观察到。这种活化过程可能具有物种特异性，类似于与沙利度胺相关的致畸特性。我们使用大鼠主动脉模型和人主动脉内皮细胞，在人、兔或大鼠肝微粒体存在的情况下将沙利度胺共同孵育。这些实验表明，在人或兔微粒体存在的情况下，沙利度胺可抑制大鼠主动脉微血管形成并减缓人主动脉内皮细胞增殖，但在大鼠微粒体存在的情况下则不然。在没有微粒体的情况下，沙利度胺对微血管形成或细胞增殖均无影响，因此表明沙利度胺的一种代谢产物是其抗血管生成作用的原因，并且这种代谢产物可在人和兔中形成，但在啮齿动物中则不然。
