Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2-mediated JAK/STAT3 signaling in endothelial cell
Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2-mediated JAK/STAT3 signaling in endothelial cell
复制标题
靛玉红通过阻断内皮细胞中 VEGFR2 介导的 JAK/STAT3 信号传导，通过抗肿瘤血管生成来抑制肿瘤生长
DOI：
10.1002/ijc.25909
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发表时间：
2011-11-15
影响因子：
6.4
通讯作者：
Yi, Zhengfang
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoli;Song, Yajuan;Yi, Zhengfang
肿瘤血管生成是恶性肿瘤发生和转移的标志之一。许多血管生成抑制剂是来自天然产物的小分子。靛玉红是传统中草药板蓝根的活性成分，已被证明具有抗肿瘤和抗炎作用。但其在肿瘤血管生成中的作用及其分子机制尚不清楚，血管生成是肿瘤生长和转移的关键步骤。在这里，我们发现靛玉红通过抑制肿瘤血管生成来抑制前列腺肿瘤生长。采用鸡胚绒毛尿囊膜（CAM）法和小鼠角膜模型，我们发现靛玉红抑制体内血管生成。靛玉红在体外对内皮细胞迁移、管腔形成和细胞存活均有抑制作用。靛玉红抑制血管内皮生长因子受体2介导的Janus激酶（JAK）/STAT 3信号通路，但对内皮细胞细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶活性影响不大。我们的研究首次为靛玉红的抗肿瘤血管生成活性及其相关分子机制提供了证据。我们的研究表明靛玉红是一种潜在的治疗血管生成相关疾病的候选药物。
Tumor angiogenesis is one of the hallmarks of the development in malignant neoplasias and metastasis. Many angiogenesis inhibitors are small molecules from natural products. Indirubin, the active component of a traditional Chinese herbal medicine, Banlangen, has been shown to exhibit antitumor and anti-inflammation effects. But its roles in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism is unknown. Here, we identified that indirubin inhibited prostate tumor growth through inhibiting tumor angiogenesis. Using chick chorioallantoic membrane (CAM) assay and mouse corneal model, we found that indirubin inhibited angiogenesis in vivo. We also showed the inhibition activity of indirubin in endothelial cell migration, tube formation and cell survival in vitro. Furthermore, indirubin suppressed vascular endothelial growth factor receptor 2-mediated Janus kinase (JAK)/STAT3 signaling pathway but had little effects on the activity of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase in endothelial cell. Our study provided the first evidence for antitumor angiogenesis activity of indirubin and the related molecular mechanism. Our investigations suggested that indirubin was a potential drug candidate for angiogenesis related diseases.