Research On Relative Property And Molecular Mechanism Of Butein Inhibiting Tumor Angiogenesis

Angiogenesis, the formation of new blood vessels upon pre-existing ones, is a complicated process orchestrated by a range of pro-angiogenesis factors and anti-angiogenesis factors. Pathologically, it will lead to a series of illnesses; among which, the most severe result is solid tumor rapid growth, progression, and metastasis. If there is no enough oxygen and nutrition delivered by new blood vessels, the tumor will halt growth when its volume reaches two to three cubic millimeters. In order to keep growing, tumor cells spread the pro-angiogenesis factors around to recruit the formation of new blood vessels. Therefore, the target of anti-tumor could be made by cutting off tumor supply lines by means of inhibiting the tumor factors or suppressing any procedure involved in angiogenesis. Compare with the traditional therapies such as chemotherapy and radiotherapy, there are a lot of advantages in anti-angiogenesis treatment in terms of curative effect and lower side effects. Therefore, the potent angiogenesis inhibitors extracted from fruits, vegetables and Chinese herb medicines which are more efficacious, less expensive, and exhibit minimum toxicity, have become important choices of drug screemng.Butein is a kind of plant polyphenols compound, which has been identified as major active component from many plants. It has been reported that butein could reduce antibody-associated glomerulonephritis. Besides, evidence indicates that butein could inhibit the proliferation of some human tumor cells in vitro. Notwithstanding, whether or not butein inhibits tumor growth by means of suppressing tumor angiogenesis and its underlying molecular mechanisms involved with angiogenesis are still unknown.Herein, though in vitro cell experiments, we present that butein could inhibit several major steps in the growth of micro vessel sprouts the size of capillary blood vessels, which are, endothelial cells proliferation, migration, trans-membrane migration and tube formation; and the inhibiting effects are dose-dependent. Taken together, butein could inhibit the early stage of angiogenesis in vitro. Moreover, we show that butein could inhibit the final formation of angiogenesis in vivo by using chick-embryo chorioallantoic membrane assay and mouse corneal micro pocket assay. In addition, we prove that butein could inhibit nude mouse tumor growth, and immune histochemistry assay further demonstrate that inhibition is accomplished by suppressing tumor angiogenesis. After that, we investigate in detail the molecular mechanisms of butein inhibiting angiogenesis by using western blot assay, and find out that butein inhibits tumor growth and tumor angiogenesis mainly though suppressing VEGFR2mediated Akt-mTOR-S6signaling pathway, and phosphorylation of FAK and ERK.The effects of butein inhibiting tumor angiogenesis and its underlying molecular mechanisms, as well as butein inhibiting mTOR signaling pathway in endothelial cells, were systematically disclosed by this study for the first time, which would lay the fundamental for further research and development of new drugs involved with angiogenesis-related diseases, and would provide better example for research on effect of Chinese herb medicine monomers inhibiting tumor angiogenesis.