Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro
Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro
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DOI：
10.1016/j.mvr.2005.01.002
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Bartlett, JB
中科院分区：
文献类型：
--
作者：
Dredge, K;Horsfall, R;Bartlett, JB
沙利度胺类似物和免疫调节药物（IMiD（R））来那度胺（CC-5013，REVLIMD（TM））正在成为许多癌症的有效治疗方法，最近已进入多发性骨髓瘤的III期试验。已经表明来那度胺的抗肿瘤作用与其抗血管生成效力有关。在这方面，我们以前已经表明，来那度胺抑制大鼠和人的体外模型中的血管生成，但不影响内皮细胞增殖。我们现在表明，口服来那度胺减弱生长因子诱导的血管生成在体内，大鼠肠系膜窗口试验被用来表明，来那度胺显着抑制血管形成的剂量依赖性方式。我们还发现，来那度胺显着抑制生长因子诱导的内皮细胞迁移。这与来那度胺对生长因子诱导的Akt磷酸化的抑制作用相关，从而为其抗迁移和随后的抗血管生成作用提供了潜在机制。这些数据进一步支持来那度胺作为口服药物用于有效治疗血管生成依赖性疾病（包括癌症），并提示了潜在的作用机制。(c)2005年爱思唯尔公司All rights reserved.
The thalidomide analogue and immunomodulatory drug (IMiD (R)) lenalidomide (CC-5013, REVLIMD (TM)) is emerging as a useful treatment for a number of cancers and has recently entered phase III trials for multiple myeloma. It has been suggested that the anti-tumor effect of lenalidomide is related to its anti-angiogenic potency. In this regard, we have previously shown that lenalidomide inhibits angiogenesis in both rat and human in vitro models but does not affect endothelial cell proliferation. We now show that oral administration of lenalidomide attenuates growth factor-induced angiogenesis in vivo; the rat mesenteric window assay was utilized to show that lenalidomide significantly inhibits vascularization in a dose-dependent manner. We also found that lenalidomide significantly inhibits growth factor-induced endothelial cell migration. This correlates with the inhibitory effect of lenalidomide on growth factor-induced Akt phosphorylation, thereby providing a potential mechanism for its anti-migratory and subsequent anti-angiogenic effects. These data further support the use of lenalidomide as an orally administered drug for the effective treatment of angiogenesis-dependent conditions, including cancer, and suggest a potential mechanism of action. (c) 2005 Elsevier Inc. All rights reserved.