Wogonin inhibits LPS-induced tumor angiogenesis via suppressing PI3K/Akt/NF-κB signaling

被引:55
|
作者
Zhao, Kai [1 ]
Song, Xiuming [1 ]
Huang, Yujie [1 ]
Yao, Jing [1 ]
Zhou, Mi [1 ]
Li, Zhiyu [1 ]
You, Qidong [1 ]
Guo, Qinglong [1 ]
Lu, Na [1 ]
机构
[1] China Pharmaceut Univ, Jiangsu Key Lab Carcinogenesis & Intervent, Key Lab Drug Qual Control & Pharmacovigilance, State Key Lab Nat Med,Minist Educ, Nanjing 210009, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Lipopolysaccharide (LPS); Wogonin; Tumor angiogenesis; PI3K/Akt/NF-kappa B signaling pathway; IN-VIVO; TYROSINE PHOSPHORYLATION; INFLAMMATION; PATHWAY; GROWTH; VEGF; HIF-1-ALPHA; ACTIVATION; EXPRESSION; APOPTOSIS;
D O I
10.1016/j.ejphar.2014.05.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However, whether wogonin inhibits [PS-induced tumor angiogenesis is not well known. In this study, we investigated the effect of wogonin on inhibiting [PS-induced tumor angiogenesis and further probed the underlying mechanisms. ELISA results revealed that wogonin could suppress [PS-induced VEGF secretion from tumor cells. Transwell assay, tube formation assay, rat aortic ring assay and CAM model were used to evaluate the effect of wogonin on angiogenesis induced by MCF-7 cell (treated with [PS) in vitro and in vivo. The inhibitory effect of wogonin on angiogenesis in [PS-treated MCF-7 cells was then confirmed by the above in vitro and in vivo assays. The study of the molecular mechanism showed that wogonin could suppress Pl3K/Akt signaling activation. Moreover, wogonin inhibited nuclear translocation of NF-kappa B and its binding to DNA. The result of real-time PCR and luciferase reporter assay suggested that VEGE expression was down-regulated by wogonin primarily at the transcriptional level. IGE-1 and p65 expression plasmid were used to activate PI3K/Akt and NE-kappa B pathways, and to observe the effect of wogonin on the simualtion of Pl3K/Akt/NE-kappa B signaling. Taken together, the result suggested that wogonin was a potent inhibitor of tumor angiogenesis and provided a new insight into the mechanisms of wogonin against cancer. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:57 / 69
页数:13
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