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The Effect And Mechanism Of Huoxuehuayu Chinese Medicine And Cryptotanshinone On Neoplasm Metastasis

Posted on:2013-12-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:L G YanFull Text:PDF
GTID:1224330482963006Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Purpose:The aim of this study is to research the different intensity of blood circulation drugs on the different induced polymerization inhibitor-induced platelet aggregation, tumor metastasis, the surface p-selectin expression on platelet activation, and to study the cryptotanshinone (CTS), the active ingredient may exist in the role of the target and mechanism of metastasis.Experimental Approach:Using human platelet aggregation experiment,we research different intensity of Huoxuehuayu herbs on platelet aggregation and on the expression of platelet activation surface p-selectin, and select three herbs to research on animal model of B16F10 cells.The we study the mechanism of the cryptotanshinone anti tumor metastasisstudy. in vitro and in vivo tumor suppression experiments, including B16F10 cell growth, migration, adhesion between platelets and MDA-MB-231 cells, platelet-mediated MDA-MB-231 cell proliferation, platelet-mediated MDA-MB-231 cell migration, B16F10 cells secreted TNF-alphacontent of B16F10 cell,and transfer model of experimental、lung tissue ICAM-1 and E-selectin molecule expression of B16F10, A549 and MDA-MB-231 cells、WNT/β-catenin signaling pathway.Experimental result:(1) Huoxuehuayu herbs aqueous extract can inhibit a variety of induced inhibitor-induced platelet aggregation, but different types, different kinds of Huoxuehuayu herbs inhibit different inhibitor-induced platelet aggregation as varying intensity, on PAF-induced platelet aggregation, inhibition from strong to weak:hexue> poxue>huoxue; ADP-induced platelet aggregation, inhibition from strong to weak:hexue> poxue>huoxue; Thrombin-induced platelet aggregation, inhibition from strong to weak are:huoxue>hexue> poxue.The concept is different from traditional.(2) Huoxuehuayu herbs aqueous extract inhibit platelet aggregation, may be related to inhibition of platelet activation, the surface p-selectin expression, inhibition from strong to weak are:poxue>huoxue>hexue.(3)Danshen and leech water extract can inhibit the B16F10 cells spontaneous tumor metastasis mouse model of lung metastases, while Chuanxiong water extract promote the transfer.(4) Cryptotanshinone, resveratrol, tanshinone Ⅱ A and so on, has good inhibition on rabbit platelet aggregation.(5)Cryptotanshinone reduce the number of B16F10 cells,inhibit B16F10, A549 and MDA-MB-231 cell migration, inhibit human platelet aggregation,adhesion between platelet and MDA-MB-231 cells, inhibit platelet-mediated MDA-MB-231 cell proliferation, inhibit platelet-mediated MDA-MB-231 cell migration, inhibit tumor cell-cell adhesion to extracellular matrix, reduce the amount of B16F10 cells secretion of TNF-α, inhibit the WNT/beta-catenin signaling pathways of B16F10, A549 and MDA-MB-231 cells.(6) Cryptotanshinone significantly inhibit B16F10 cells in experimental tumor metastasis model of C57BL/6 mice lung metastases by gavage and intraperitoneal injection, inhibit ICAM-1 and E-selectin expression in the mouse lung tissue of experimental metastasis model, reduce serum content of TNF-a of mice in B16F10 cells experimental metastasis model.Conclusion and significance:This study found that:1. different huoxuehuayu herbs can inhibit platelet aggregation induced by different inhibitor, possibly through the inhibition of platelet surface p-selectin expression.2.Danshen and leech water extract can inhibit tumor metastasis, while the the Chuanxiong water extract promote the transfer, in the clinical, huoxuehuayu herbs must be used with caution.3. Cryptotanshinone can inhibit platelet aggregation, inhibit tumor cell migration, inhibit the adhesion of platelets and tumor cells, inhibition of platelet-mediated tumor cell proliferation and platelet-mediated tumor cell migration, inhibit tumor cell-cell adhesion to extracellular matrix,inhibit experimental metastasis of B16F10 cells, may be connected with inhibition of platelet surface p-selectin expression, reduction B16F10 cells TNF-alpha, reduction of ICAM-1 and E-selectin molecules, and cryptotanshinone can inhibit WNT/beta-catenin pathway, inhibit tumor cells in Wnt3a and (3-catenin expression, and enhance the expression of E-cadherin and Axin, and reduce the adhesion of platelets and tumor cells, resulting in anti-tumor metastasis.
Keywords/Search Tags:huoxuehuayu herbs, platelets, tumor metastasis, adhesion, B16F10, A549, MDA-MB-231, WNT/beta-catenin
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