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The Experimental Study On Anti-tumor Mechanism Of Duchesnea Inhibit The Activity Of Matrix Metalloproteinases-13

Posted on:2011-12-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhaoFull Text:PDF
GTID:2144360305955325Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
The tumor is the general name that modern medicine to organism internal organs organization neoplasm,the malignant tumor is called cancer. Malignant tumor is one of the main diseases arousing human being death at present. In the process of growth malignant tumor, it is able to infiltrate vicinity organization or metastasize to the body's other location. This infiltration and transfer are the important feature of malignant tumor,they are also the main causes that tumor patients dies and tumor treatment failure,with tumor transfers of which the most serious. In known malignant tumor,besides the skin basal cell carcinoma and some of the central nervous system tumors rarely metastasize,most other progress of the disease can metastasize. Tumor metastasis is a complex process,there are different regulatory mechanisms involved in many processes,in which extracellular matrix (ECM) and tumor metastasis are extremely close relationship. It has been confirmed that ECM is a barrier to prevent tumor metastasis. In the process of tumor infiltration and metastasis,the tumor cell has had a series of dynamic changes with the periphery outside matrix. In this process,it has the releasing of matrix metalloproteinase (MMPs),catepsin and plasmase, it has the synthesis and degeneration of W collagen,the level adhesion protein,the gelatin protein,the textile fiber connection protein as well as outside other matrix ingredient,it also has the participation and adjustment of collagenase inhibitor TIMP-1,TIMP-2 and adherency member,simultaneously also has the tumor cell to release the fibroblast growth factor,blood vessel endothelial cell growth factor and vascularization inhibiting factor to mediate tumor vascularization and so on. Therefore the ECM degeneration definitely will promote the tumor's infiltration and transfer. ECM mainly includes five major kinds of matter,which is the collagen , the protein polysaccharide , the glycoprotein , the osamine polysaccharide and the elastic fibers and so on. The collagen is the most abundant ECM components. The ECM degradation enzyme have 6 major kinds at least:(1) Prolinase , (2) Serine protease , (3) Cysteine protease , (4) Asparagus cochinchinensis acidamides protease,(5) Glycosidase,(6) MMPS. And MMPs has the widespread degeneration function to ECM,is the most important enzymatic system that adjusts the ECM's dynamical equilibrium. Expression and activation of MMPs are related to tumor growth,invasion and metastasis,which is frequent over-expression in malignant tumors. In tumor growth,invasion, metastasis and angiogenesis,by inhibiting the activity of MMPs is clearly an extremely important new target for treatment of malignant tumors. China's traditional herbal medicine,Duchesnea,commonly used as a civil,has huayu swelling,heat detoxification,convergence of bleeding,cooling blood and other effects. It was found significant anti-tumor activity, in the clinical treatment of cancer had also shown good results in recent years. But so far,the chemical composition and biological activity of coverage about Duchesnea is still very limited, its composition and anti-tumor mechanism is not clear. In addition,the Duchesnea is a herb widely distributed in China and easy cultivation of reproduction,which provide a rich plant resources for further research and development and utilization. Therefore,we believe that Duchesnea is a very worthwhile development and utilization of plant resources,especially in research on antitumor drugs,with good development prospects. Clinical pharmacology studies have shown that Duchesnea has a clear anti-tumor effect. The author wants through this experiment to confirm whether the Duchesnea treat tumor is related to inhibiting the MMPs'activeness.Methods:Be 1μl of the MMP-13 and 1μl of different concentrations of Duchesnea extract added to 48μl of the buffer solution,to make the final volume of 50μl, the control group did not join the Duchesnea solution. Solution in each group will then join the 96-hole ELISA plate,and be put into the 37℃incubator and incubated for 30 minutes,then add 0.2μg DQ-gelatin containing a buffer solution of 50μl,100μl final reaction system for the two groups,and then immediately with the Bio-Red FLx-800 fluorescence microplate reader to detect, excitation wavelength of 460nM emission wavelength of 520nM,detection of 10 minutes. Detection of changes in fluorescence intensity represents the enzymatic strength of degrading the substrate activity. By inhibiting the activity of the calculation,Observed Duchesnea extracts on inhibition of MMP-13. When the inhibition percentage of 50%,compared with Duchesnea extracts inhibit enzyme activity of IC50. Results:The Duchesnea water extraction has the inhibitory action in vitro to MMP-13,IC50=1.15μg/ml. And this kind of inhibitory action has the dosage dependence that Duchesnea water extract of the inhibition of MMP-13 associated with the drug concentration.Conclusion:Duchesnea water extract can inhibit the activity of MMP-13,and it has strong inhibition. The higher Duchesnea concentration is,the better its inhibitory effect to MMP-13 is. This further confirm that looking for new drugs from the natural medicine in order to MMPs / TIMPs as a therapeutic target has broad prospects.
Keywords/Search Tags:Duchesnea, matrix metalloproteinase, tumor
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