Journal
PLOS ONE
Volume 10, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0117440
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Funding
- Chongqing Natural Science Foundation [CSTC2013jjB10007]
- National Natural Science Foundation of China [81402970]
- State Key Laboratory of Silkworm Genome Biology, Southwest University [2013024]
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Hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) play important roles in angiogenesis and tumor growth. Tanshinone IIA (T2A) is a novel antiangiogenic agent with promising antitumor effects; however, the molecular mechanism underlying the antiangiogenic effects of T2A remains unclear. In the present study, we provided evidence showing that T2A inhibited angiogenesis and breast cancer growth by down-regulating VEGF expression. Specifically, T2A repressed HIF-1 alpha expression at the translational level and inhibited the transcriptional activity of HIF-1 alpha, which led to the down-regulation of VEGF expression. Suppression of HIF-1 alpha synthesis by T2A correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), a pathway regulating HIF-1 alpha expression at the translational level. In addition, we also found that T2A inhibited the angiogenesis and growth of human breast cancer xenografts in nude mice through suppression of HIF-1 alpha and VEGF. Our study provides novel perspectives and potential targets for the treatment of human breast cancer.
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