血管生成
癌症研究
转移
STAT蛋白
新生血管
车站3
癌症
血管内皮生长因子
肿瘤进展
医学
血管内皮生长因子A
下调和上调
肿瘤微环境
信号转导
癌细胞
生物
内科学
血管内皮生长因子受体
细胞生物学
生物化学
基因
作者
Xinxin Wu,Tao Yang,Xiang Liu,Jia Nian Guo,Tingting Xie,Yuan-Wei Ding,Manpeng Lin,Hui Yang
出处
期刊:Tumor Biology
[SAGE]
日期:2015-11-13
卷期号:37 (4): 5493-5501
被引量:58
标识
DOI:10.1007/s13277-015-4372-4
摘要
Gastric cancer is the world’s second most common malignancy and is a major threat to global health. IL-17, a CD4 T cell-derived mediator of angiogenesis, plays a major role in stimulating angiogenesis by regulating the production of a variety of proangiogenic factors, including the vascular endothelial growth factor (VEGF). The level of VEGF expression correlates with tumor progression and metastasis in gastric cancer tissues. Abnormal activation of signal transducer and activator of transcription 3 (Stat3) rendered the tumor cells highly angiogenic, which is manifested by an increased microvascular density (MVD) and considered it as a potential molecular marker for poor prognosis in gastric cancer angiogenesis. We determined that IL-17A-induced VEGF upregulation and neovascularization through a Stat3-mediated signaling pathway and hypothesized that blocking the Stat3 activation by using JSI-124, an inhibitor of phosphorylated Stat3, could significantly reduce the VEGF expression and can thus prevent angiogenesis. We showed an inhibition of angiogenesis and tumor progression when JSI-124 was treated with IL-17A in the cells and xenografts in an animal model and suggested that targeting the Stat pathway with JSI-124 could derive an effective therapeutic target for gastric cancers and could be a promising drug in gastric cancer treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI