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      1. Author :
        Sui, Hua; Zhao, Jihui; Zhou, Lihong; Wen, Haotian; Deng, Wanli; Li, Chunpu; Ji, Qing; Liu, Xuan; Feng, Yuanyuan; Chai, Ni; Zhang, Qibo; Cai, Jianfeng; Li, Qi
      2. Title :
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        Cancer Letters
      6. Products :
      7. Volume :
      8. Issue :
      9. Page Numbers :
      10. Research Area :
      11. Keywords :
        Tanshinone IIA; Colorectal cancer; Hypoxia; Angiogenesis; β-catenin/TCF/LEF signaling pathway; TGF-β; HIF-1α; IVIS; IVIS BLI in vivo
      12. Abstract :
        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-NH2) and found that it effectively targets HIF-1α overexpression in a mouse colon tumor model. Finally, Tan IIA sodium sulfonate exhibits anti-angiogenesis activity in CRC patients by reducing levels of angiogenin, VEGF and bFGF expression. Our research provides a new anti-angiogenesis strategy and strengthens support for the use of Tan IIA as an angiogenesis inhibitor.
      13. URL :
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13972
      15. Serial :