Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
J Pharmacol Sci. 2020 Jun;143(2):122-126. doi: 10.1016/j.jphs.2020.02.010. Epub 2020 Mar 3.
Tumor blood vessels have leaky and low blood flow properties, which lead to hypoxia and low nutrient levels in the tumor tissue area known as the tumor microenvironment (TME). We reported that the prolyl-hydroxylase (PHD) inhibitor Roxadustat normalized tumor blood vessels, improved tumor tissue perfusion, and re-oxygenated the tumor tissue. Recently, several PHD inhibitors including Roxadustat, Daprodustat, Molidustat, and Vadadustat, were evaluated in clinical trials and approved for treating renal anemia. In this study, we showed that PHD inhibitors reconstituted tumor blood vessels and improved the TME, and some agents exhibited differential effects on tumors in a mouse model.
肿瘤血管具有渗漏和低血流的特性，导致肿瘤组织区域缺氧和营养水平低，即肿瘤微环境（TME）。我们曾报道过脯氨酰羟化酶（PHD）抑制剂罗沙司他可使肿瘤血管正常化，改善肿瘤组织灌注，并重新为肿瘤组织供氧。最近，几种 PHD 抑制剂，包括罗沙司他、达普司他、莫立司他和伐达司他，在临床试验中进行了评估，并被批准用于治疗肾性贫血。在这项研究中，我们表明 PHD 抑制剂可重建肿瘤血管并改善 TME，并且一些药物在小鼠模型中对肿瘤具有不同的作用。
