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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Tanshinone IIA inhibitsβ-catenin/VEGF-mediated angiogenesis by targeting TGF-β1 in normoxic and HIF-1α in hypoxic microenvironments in human colorectal cancer.

Abstract Source:

Cancer Lett. 2017 09 10 ;403:86-97. Epub 2017 Jun 7. PMID: 28602978

Abstract Author(s):

Hua Sui, Jihui Zhao, Lihong Zhou, Haotian Wen, Wanli Deng, Chunpu Li, Qing Ji, Xuan Liu, Yuanyuan Feng, Ni Chai, Qibo Zhang, Jianfeng Cai, Qi Li

Article Affiliation:

Hua Sui

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 endothelialcell 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) 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.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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