angiogenin and tanshinone

In a previous study, we demonstrated that Tanshinone IIA effectively inhibits CRC angiogenesis in vivo, but the underlying mechanisms were not elucidated. In this report, we describe experiments in which HIF-1α levels were manipulated to probe the effect of hypoxia on CRC cell angiogenesis. We studied the effects of Tan IIA on CRC pro-angiogenic factor and on human umbilical vein endothelial cell angiogenesis in normoxia and hypoxia. Our results show that Tan IIA not only lowers HIF-1α levels and inhibits secretion of VEGF and bFGF, but also efficiently suppresses the proliferation, tube formation and metastasis of HUVECs. Interruption of the HIF-1α/β-catenin/TCF3/LEF1 signaling pathway occurs in the hypoxic microenvironment. The mechanism involves HIF-1α inhibition of TGF-β1 secretion, which drives angiogenesis by promoting β-catenin nuclear localization and TCF/LEF activation. To test an improved delivery system for Tan IIA, we loaded the drug into mesoporous silica nanoparticles (MSN-NH

Topics: Abietanes; Angiogenesis Inhibitors; Animals; Basic Helix-Loop-Helix Transcription Factors; beta Catenin; Cell Movement; Cell Proliferation; Chick Embryo; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Fibroblast Growth Factor 2; HCT116 Cells; HT29 Cells; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphoid Enhancer-Binding Factor 1; Male; Mice, Nude; Middle Aged; Neovascularization, Pathologic; Neovascularization, Physiologic; Ribonuclease, Pancreatic; Signal Transduction; Transfection; Transforming Growth Factor beta1; Tumor Burden; Tumor Hypoxia; Tumor Microenvironment; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays