期刊
ONCOTARGETS AND THERAPY
卷 8, 期 -, 页码 427-435出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S76116
关键词
Andrographolide (Andro); HIF-1 alpha; inhibit; breast cancer; hypoxia; PI3k/AKT/mTOR pathway
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. HIF-1 alpha 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 1.03x10-7 mol/L), by a dual-luciferase reporter assay. It suppressed HIF-1 alpha 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.
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