Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 737, Issue -, Pages 57-69Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2014.05.011
Keywords
Lipopolysaccharide (LPS); Wogonin; Tumor angiogenesis; PI3K/Akt/NF-kappa B signaling pathway
Categories
Funding
- National Natural Science Foundation of China [91029744]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT1193]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGZ201101, SKLNMZZ201210, SKLNMZZCX201303, SKLNMZZJQ201302]
- Fundamental Research Funds for the Central Universities [JKP2011003]
- The National Science & Technology Major Project [2012ZX09304-001]
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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.
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