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Study On The Inhibition By The Medicated Serum With Scutellariabarbatae D.Don Of Cancer Angiogenesis

Posted on:2006-09-28Degree:MasterType:Thesis
Country:ChinaCandidate:N N ZhangFull Text:PDF
GTID:2144360152992593Subject:Traditional Chinese Medicine
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Angiogenesis consists of the formation of new capillaries through sprouting or splitting from preexisting cessels. In 1970 Science Dr. Judah Folkman hypothesized that angiogenesis was obligatory for tumor growth. This observation has led to the realization that blood vessels are essential for tumor growth, invasion, and metastasis. Angiogenesis is known to be a complex process that requires endothelial cell proliferation, migration and differentiation into tube-like structures and controlled by extensive interactions between a various peptides and other modulating factor produced by host or tumor cell, more and more scientists have been studying natural and synthetic angiogenesis will prevent the growth of cancer by blocking the formation of new vessels. Anti-angiogenesis therapy has become the focus of cancer research.The research on traditional Chinese medicine targeted to angiogenesis just starts in our country. No domestic reports has been published on the research on the cellular and molecular mechanisms of inhibiting the angiogenesis of cancer by anticancer single herbs.Using serum pharmacological method, we selected Scutellaria barbatae D. Don , the antiangiogensis drug from the Chinese herbral medicines which have been proved to be effective anticancer in clinic, endothelial cell tube formation experiment, Matrigel in vivo assay , endothelial cell wound healing Assays were adopted to evaluated the anti-angiogenesis effects of Scutellaria barbatae D. Don . in an attempt to study the mechanism, we used Transwell chamber, ELISA, Reporter gene assays on cell and organ level.The main result and conclusion showed as below:1. experiment of drug selection: with the same dose, the medicated serum with Scutellaria barbatae D. Don and Sparganium stoloniferum Buch Ham obviously inhibited microvascular formation in Matrigel, decrease the tube formation in vitro. Both of them can inhibit the endothelial cell migration, there was not different between the medicated serum with Rhubarb anddrug-free serum.2 the tube formation in vitro: the serum with Scutellaria barbatae D.Don of 20% concentration showed significant inbition including decrease of the tube number, tube disfunction and so on, in contrast to the control group (P<0.01)3 Transwell chamber assay: treated by the the medicated serum with Scutellaria barbatae D. Don, less number of HUVEC immigrat to the lower chamber than that of control group (P<0. 05) with dose-effect correlation.4 ELISA assay: VEGF165 expression in HeLa cell was markly inhibited by the serum of 40% concentration after 24h and 48h . But not in a time dependent manner. With the same concentration, there are the significant differences in the inhibition of VEGF165 expression between 48h and 12h (P<0. 01). with the serum of 10% concentration, there are the significant differences between 24h and 12h(P<0.01). but there are no significant differences between 24h and 12h.5. Reporter gene assays: the the medicated serum with Scutellaria barbatae D. Don of 40% concentration could significantly decrease luciferase expression in the transfected ECV-304 after hypoxic treatment, in contrast to the control group (P<0.01).conclusion: the medicated serum with Scutellaria barbatae D. Don can inhibit tumor angiogenesis ,its mechanism was probably related to theinhibition of HIF and the endothelial cell immigration. Scutellaria barbatae D. Don could be developed as an anti-angiogenic drug. At the same time, the research expore a new way in developing effective TCM and extracts for anti-angiogenesis therapy.
Keywords/Search Tags:Scutellaria barbatae D. Don, the medicated serum, angiogenesis, tumor, human umbilical vein endothelial cell, vascular endothelial growth factor, hypoxia induced factor
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