硫唑嘌呤的抗血管生成活性。

Anti-angiogenic activity of azathioprine.

作者信息

de Melo Bisneto Abel Vieira, Fernandes Amanda Silva, Velozo Sá Vivianne de Souza, Véras Jefferson Hollanda, Soares Estéfane Thaíne Sodré, da Silva Santos Aline Ferreira, Cardoso Clever Gomes, Silveira-Lacerda Elisângela de Paula, Carneiro Cristiene Costa, Chen-Chen Lee

机构信息

Laboratory of Radiobiology and Mutagenesis, Department of Genetics of Institute of Biological Sciences, Federal University of Goiás, 74690-900 Goiânia, Brazil.

Laboratory of Molecular Genetics and Cytogenetics, Department of Genetics of Institute of Biological Sciences, Federal University of Goiás, 74690-900 Goiânia, Brazil.

出版信息

Microvasc Res. 2021 Nov;138:104234. doi: 10.1016/j.mvr.2021.104234. Epub 2021 Aug 31.

DOI:10.1016/j.mvr.2021.104234

PMID:34478745

Abstract

Azathioprine (AZA) is the main drug used in immunomodulatory therapy in post-transplant patients or with autoimmune diseases. However, no study has evaluated the AZA angiogenic response. Therefore, this study investigated the effects of AZA on the angiogenic process through macroscopic, histological, and immunohistochemical analyses in chick embryo chorioallantoic membrane (CAM). Our results showed potent anti-angiogenic activity of AZA at the higher concentrations tested in the CAM assay. The histological analysis of CAM confirmed this effect, since AZA induced a significant reduction in all parameters evaluated. In addition, immunohistochemical evaluation of CAM revealed that AZA decreased TGF-β and VEGF levels, important cytokines involved in the angiogenic process. Therefore, the AZA anti-angiogenic effect identified in our study provides new information for the possible application of this drug in anticancer treatment.

摘要

硫唑嘌呤（AZA）是移植后患者或自身免疫性疾病患者免疫调节治疗中使用的主要药物。然而，尚无研究评估AZA的血管生成反应。因此，本研究通过对鸡胚绒毛尿囊膜（CAM）进行宏观、组织学和免疫组织化学分析，研究了AZA对血管生成过程的影响。我们的结果显示，在CAM试验中测试的较高浓度下，AZA具有强大的抗血管生成活性。CAM的组织学分析证实了这一效果，因为AZA导致所有评估参数显著降低。此外，CAM的免疫组织化学评估显示，AZA降低了TGF-β和VEGF水平，这两种是血管生成过程中重要的细胞因子。因此，我们研究中确定的AZA抗血管生成作用为该药物在抗癌治疗中的可能应用提供了新信息。