Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor
Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor
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DOI：
10.1038/nm0202-128
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发表时间：
2002-02-01
期刊：
影响因子：
82.9
通讯作者：
Geissler, EK
中科院分区：
文献类型：
--
作者：
Guba, M;von Breitenbuch, P;Geissler, EK
传统的免疫抑制药物已被有效地用于预防器官移植中的免疫排斥反应。然而，服用这些药物的人有患癌症和复发的风险。在目前的研究中，我们表明新的免疫抑制药物雷帕霉素(RapA)可以降低癌症发展的风险，同时提供有效的免疫抑制。在实验上，RAPA抑制了体内小鼠模型中转移瘤的生长和血管生成。此外，正常免疫抑制剂量的RAPA有效地控制了已建立的肿瘤的生长。相比之下，最广为人知的免疫抑制药物环孢素促进了肿瘤的生长。从机制的角度来看，RAPA显示出与血管内皮生长因子(VEGF)的产生减少以及血管内皮细胞对血管内皮生长因子刺激的反应明显抑制有关的抗血管生成活性。因此，在高危移植患者中，使用RAPA而不是环孢菌素，可能会降低复发或复发的几率。
Conventional immunosuppressive drugs have been used effectively to prevent immunologic rejection in organ transplantation. Individuals taking these drugs are at risk, however, for the development and recurrence of cancer. In the present study we show that the new immunosuppressive drug rapamycin (RAPA) may reduce the risk of cancer development while simultaneously providing effective immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses of RAPA effectively controlled the growth of established tumors. In contrast, the most widely recognized immunosuppressive drug, cyclosporine, promoted tumor growth. From a mechanistic perspective, RAPA showed antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients.