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The Experimental Study on Anti-tumor Mechanism of Rhizoma Paridis Inhibit the Activity of Matrix Metalloproteinases-16

Author: AnXuChen
Tutor: ZhaoShuHua
School: Jilin University
Course: Traditional Chinese Medicine
Keywords: Paridis Matrix metalloproteinase Tumor
CLC: R285
Type: Master's thesis
Year: 2011
Downloads: 55
Quote: 2
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Abstract

Malignancies is currently one of the serious diseases that endanger human life and health, and how to prevent and treat cancer, is still a major problem facing humanity in the 21st century, the development and the development of anticancer drugs has become an important topic in recent years. Tumor invasion and metastasis of tumor cells from the primary tumor out of the process of invasion and metastasis to the surrounding or distant tissues involved in tumor cells through the extracellular matrix barrier basement membrane of the blood vessel wall and the wall wearing bleeding into the host microenvironment process. A large number of experiments show that tumor cell invasion and metastasis of their induction to produce protease degradation of extracellular matrix and basement membrane's ability to closely related. Matrix metalloproteinases that can degrade almost all ECM components, and tumor invasion the transfer relationship largest enzymes. MMPs are a the ECM proteolytic enzyme, the ECM structural components of the diversity and complexity of the cell function, MMPs also inevitably affect the degradation of ECM proteins differentiation, morphology and function of the cell signal transduction and cell. Therefore, MMPs by degradation of ECM components to regulate the homeostasis of degradation between the substrate and the recombinant protein in order to achieve the elimination of certain special signals appeared implicit signal release or activation, so that the presence of biologically active substances in the matrix, and further a variety of morphological and functional changes in cells and tissues and organs. An MMP can be directly the degradation of one or several ECM, through the activation of other types of MMPs can also play a role. MMPs are mainly three kinds of mechanisms to promote the growth of tumor cell invasion: ① The protease role makes tumor cells surrounding matrix molecules to form the physical barrier is destroyed; ② The of MMPs can enhance cell adhesion force, so that the tumor cells to the surrounding growth; ③ The of MMPs role in matrix components After inspire other potential biological activity. Inhibitors of MMPs, including non-specific inhibitors, tissue-specific inhibitors (TIMPs), and synthetic inhibitors. TIMPs are specific inhibitors of MMPs, and plays the most important role in the regulation of activity of MMPs. TIMPs are secreted by the cells in vivo, can inhibit the activity of MMPs, the zymogen with the MMPs to an activated form of a combination of endogenous tissue-specific inhibitors. TIMPs in tumor cells and stromal cells can express. TIMPs's main function is to inhibit the activity of MMP; hinder MMP-mediated endothelial cell migration; inhibiting the release of angiogenic factors in the matrix, inhibition of angiogenesis; to prevent the degradation of extracellular matrix. Therefore, whether from traditional Chinese medicine to develop new inhibitors of MMPs is a new breakthrough. Antineoplastic agents is both current domestic an important part of the modernization of Chinese medicine extracted from natural plant abroad the basis of clinical medicine research hotspot. The synthesis of many anti-cancer chemotherapy drug, the development costs are expensive, toxic side effects, even of its own with carcinogenic toxicity caused by the occurrence of the second tumor; herbs, botanicals and other natural products, there is a wide range of biological activity substances, Chinese medicine dialectical theory of governance, the principle of the overall treatment is very effective in the treatment of cancer, so people turned to look at the natural world, looking for drug side effects and the unique role of anticancer drugs and anti-tumor auxiliary drugs from natural products. A large number of epidemiological investigation confirmed that many herbs have a very important role in the prevention and treatment of cancer, has anti-tumor and regulation of the immune function of natural plant is expected to become important resources of anticancer drugs, and there are broad prospects for the development and application value. Especially Chinese herbal source of a wide range, variety, according to incomplete statistics, derived from botanicals anticancer agents, accounting for 32.25% of the anti-cancer drugs, such as yew drunk, tea alkali, vincristine has been widely accepted at home and abroad, as the drug of choice for the treatment of certain tumors. The pharmacological effects Paridis studies have confirmed that it has a clear anti-tumor effect, and extracted a variety of chemical ingredients have been confirmed to have a clear anti-tumor activity, so the authors would like to be confirmed by the experimental re-floor the treatment of tumors to their inhibition of the activity of MMPs related to the purpose of the experiment: observation of the water extract of Chinese medicine Paridis whether inhibition of MMPs exist to provide the necessary theoretical and experimental basis for the pharmacological mechanisms of the traditional Chinese medicine treatment of cancer of the heavy floor. Experimental Methods: a certain amount of MMP-16 solution were added to the enzyme reaction buffer solution and heavy floor water extract 5mg/mL, 4mg/mL, 2mg/ml, 1mg/ml, 0.5 mg / mL and 0.25mg/mL concentration solution, incubated for 30min after adding 0.2μgDQ-gelatin substrate detection. The detected change in fluorescence intensity that is representative of the enzymatic degradation of the dynamic strength of the substrate. Experimental Principle: The enzymatic degradation of the fluorescent substrate will fluoresce, detecting the change in fluorescence intensity can determine the activity of the enzyme. Fluorogenic substrate used in the experiment for the DQ-gelatin, this substrate labeled with a fluorophore, when the enzyme cleavage substrate, enzyme ends with a fluorophore and quencher moiety are separated, which emits fluorescence, and in within a certain range, the fluorescence intensity of the enhanced speed and the relationship of the enzyme reaction rate is proportional to and therefore the rate of increase of fluorescence available to represent the enzyme activity. Results: the water extract of the heavy floor in vitro MMP-16 inhibition, and this inhibition exists a dose-dependent, i.e. the heavy floor water extract on the inhibition of MMP-16 is enhanced with the increase of drug concentration. This is further confirmed by looking from the natural medicine MMPs / TIMPs as therapeutic targets for new drugs has broad prospects.

The Experimental Study on Anti-tumor Mechanism of Rhizoma Paridis Inhibit the Activity of Matrix Metalloproteinases-16

Abstract

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