Oligomer procyanidins (F2) repress HIF-1α expression in human U87 glioma cells by inhibiting the EGFR/ AKT/mTOR and MAPK/ERK1/2 signaling pathways in vitro and in vivo
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Hong-Li Zheng1,3, Li-Hui Wang1,3, Bao-Shan Sun2,4, Yi Li1,3, Jing-Yu Yang1,3 and Chun-Fu Wu1,3
1Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, P.R. China
2Department of Enology, Shenyang Pharmaceutical University, Shenyang, P.R. China
3Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi, P.R. China
4Viticultural and Enological Research Unit-National Institute for Agricultural and Veterinary Research, Dois Portos, Portugal
Chun-Fu Wu, email: firstname.lastname@example.org
Jing-Yu Yang, email: email@example.com
Keywords: F2, HIF-1α, angiogenesis, invasion, U87 glioma cell
Received: September 13, 2016 Accepted: May 31, 2017 Published: July 28, 2017
Hypoxia-inducible factor-1 (HIF-1) is over-expressed in gliomas and has become one of the most compelling tumor targets. In this study, we found that oligomer procyanidins (F2) can suppress the expressions of HIF-1α and its target genes in U87 cells, and also down-regulate the EGFR/PI3K/AKT/mTOR and MAPK/ERK1/2 pathways in vitro and in vivo. Furthermore, hypoxia-induced formation of tubular structures by human umbilical vascular endothelial cells and the migration and invasion of U87 cells could be inhibited by F2 in a HIF-1 dependent manner. Moreover, in a U87 xenograft tumor model, F2 significantly reduced intra-tumor vessel density and cell proliferation and finally retarded tumor growth, indicating that F2 may be a potential HIF-1 inhibitor and serve as one of candidates for glioma therapy.
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