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穿心莲内酯通过激活磷脂酰肌醇 3-激酶抑制低氧诱导因子- 1/AKT 的通路，并抑制乳腺癌的生长

 

Authors Li J, Zhang C, Jiang H, Cheng J

Published Date February 2015 Volume 2015:8 Pages 427—435

DOI http://dx.doi.org/10.2147/OTT.S76116

Received 20 October 2014, Accepted 7 January 2015, Published 13 February 2015

Approved for publication by Professor Jianmin Xu

Abstract: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro) was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10-7 mol/L), by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF) gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.
Keywords: Andrographolide (Andro), HIF-1α, inhibit, breast cancer, hypoxia, PI3k/AKT/mTOR pathway






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