The Mechanism Research Of Obscured Homalomena Rhizome Accommodates The Imbalance Of Matrix Metalloproteinase System In Gastric Cancer

Stomach cancer is one of the common human malignant tumors, and has the second highest tumor incidence rate and cancer mortality rate worldwide .The development of stomach cancer is a multi-step and progressive process, and there are many factors involved in the pathogenesis .The key step is that the cancer cells have to cross through the basement membrane, and invade and break down the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases(TIMPs)play very important roles in the degradation of basement membrane and ECM. A number of studies have demonstrated the role of MMP-2.7 .9 and their inhibitors in stomach cancer ,however ,there are very few studies regarding to MMP-1 and TIMP-1. Recently, it has been reported that as the first identified MMP,MMP-1 is expressed in the later stages of many cancers ,and the increase of its expression is related to the poor prognosis of many tumors. MMPs and theirs inhibitors (Tissue Inhibitor of MetalloProteinases,TIMPs)investigated recently are a series of multi一functional family factors,which could degrade ECM and inhibit the activity of MMPs.MMPs and TIMPs distribut widespread in various tissues a number of MMPs have been identifid but only four members of TIMPs are identified.I adopt DQ-gelatin substrate as fluorescence substrate in this experiment,MMP-16 fluoresces before degrading the substrate,detecting the transmutation of the fluorescence intensity in the reaction system.The determination of inhibiting action is adding the homalomenae extractive in the reaction system,the inhibiting composition in the extractive cohere with MMP-16,occupying the active center of MMP-16,making the the substrate shouldn't cohere with MMP-16,inducing the velocity of degrading substrare lower and the change of fluorescence intensity stepping down.I couled get the status that the extractive of homalomenae inhibite MMP-16 by the change of fluorescence intensity representing the vital force that MMP-16 degrades the substrate.We should yield that the%inhibition that different concentration of homalomenae extractive inhibiting MMP-16.The experimental result indicates that there is the inhibitory action that the extractive of homalomenae acts on MMPs.Matrix metalloproteinase is one member in zinc peptidase, it is an indispensable enzyme in composing connective tissue extracellular matrix degradation process. It can almost degradate all the compositions of extracellular matrix. The specific catastaltica of TIMP is a negative moderator to MMP in ECM's metabolic regulation. The system of MMP/TIMP has significant function in many physiological and pathological processes in vivo, its disharmony may mediate the occurrence of nephritis, tumor metastasis, artherosclerosis, multi-connective tissue diseases and important organs fibrous degeneration etc. Searching the new drugs as the curative target of MMP/TIMP is becoming of the hot spot in interior and exterrior exploitation. At present, several kinds of broad-spectrum and low molecular number of MMP's catastaltica are used in some kinds of tumor therapy are assessed in clinic. Altough these micromoecule medicines can high performance inhibit activity of MMP and prevent tumors'growth and diversion in preclinical animal experiments, their expensive price and fervent side effect in clinic lead to the failure in anaphase clinic. The reason is possibly because of their weak specificity. They influence many other kinds of the normal physiologic function of MMP in different extent. The clinical application of homalomenae in our country has been longstanding.And the experiment indicates that homalomenae strongly inhibits the MMP-16 activity.So we may presume that its ability of anti-tumor is correlated with its ability of inhibiting the overexpression of MMPs in body.It estab-lishes foundation that why pinelliae tuber has the ability of anti-tumor in molecular level.We may abstract MMP inhibitor from homalomenae ,then it will be true that we can explore new traditional Chinese drugs aiming to MMPs.