Experimental Study On Fineleaf Schizonepeta Herb Inhibiting MMPs On The Therapy Of Tumor

Malignant tumor is one of the main diseases that threatens human health and life,WHO and every country government Ministry of Public Health are classified as a most important mission to cure Malignant tumor.In China about two million people caught tumor and about one million and forty thousand people died of Malignant tumor every year.Developing effective medicine that can cure malignant tumor has already got common attention of the whole world. Foreign countries have already developed several kinds of broad-spectrum,low molecu- lar weight matrix metalloproteinase inhibitor used in several types of malignant tumor's treatment, and the matrix metalloproteinase inhibitor has already been clinical assessed. The small molecule drugs can highly effectively suppress the matrix metal proteinase's activity and effectively prevent malignant tumor's growth and metastasis in the pre-clinical animal experimentation, but the effect of malignant tumor's treatment is not ideal in the clinical experiment, it appears intense side effect, and its price is expensive, causes clinical defeat finally[2].More and more clinical practices prove that used Chinese materia medica or conbined treatment of traditional Chinese medicine and western medicine cure Malignant tumor got a well curative effect and to ease harm and said effect of radiotherapy and chemotherapy, also sexual valence got higher, their good qualities identified by medical science group.Traditional Chinese medicine cure Malignant tumor is a peculiarity in Malignant tumor therapeutics domain. In traditional chinese medicine,tumorigeneis- is the result of deficiency of blood and viscera dysfunction.The four basic rules on the therapy of tumor by traditional chinese medicine is promoting blood circulation by removing blood stasis,clearing heat and expelling miasma, softening hard lumps and dispel nodes and supporting healthy energy.Consult a lot of ancient medical science books and clinical data,fineleaf schizonepeta herb was recorded to dissipate blood stasis,break stagnation of QI and remove sore,and had significant therapeutic action with tumor especially with lung cancer.ECM accommodates cell Morphologic change and every kind of Normocellular's biological behaviour. A great quantity of empirical study manifest that cancer cell's ability of infestation and metabasis has close correlation with the ablity of it generates or induces to produce degrdn ECM's prolease. In the process of cancer cell infestates basal lamina, proteinum catabolic enzymes degrdns ECM has been confirmed by amounts of experimenta- tions. Regards of ECM degradation's prolease and its repressor mainly to point at metalloprotease MMPs. The major effect of MMPs in the process of metabasis is it makes for demolishing the physics barrier shield of metastatic thus makes to take place of metabasising, intravasation or absorbent vessels. In the process of tumorous growth(primarily and metabasis part) MMPs also plays an important role in regulation. MMPs is a secreting type transmembrane protein family,including collagenase, gelatinase and stromlysin,they react concomitancly, decompose ECM's every specific composition,in the physiological condition,they can digest extracellular matrix and basal lamina. MMPs mainly has three hypotypes,have been discriminated by their groundmasses (substrates) specificities:collagenase degrdn fiber collagen protein,stromlysin cums glycoprotein and proteoglycan as substration, gelatinase has specific actions in degrdning unfiber and metamorphic collagen protein.In a word,collagen protein in unactivation form excretes quickly and participates ectoactivities, proleases paiallel consists of the other MMPs family members and other kinds of zymoids'activities;once enzymes were acti- vated,they were easily abaissemented by general purpose serum proteinase inhibitorα2– macroglobulin and familial idiosyncr- atic tissue suppressor factor. MMPs nearly can degrdn each proteinum component of ECM,demolish tumour cell invasive histology barrier shield,in the process of tumor infestation and metabasis, they play an criticality role,accordingly the effection in the process of tumor infestation and metabasis has been increasingly reconstructed, and known as the main enzyme in this process. MMP-13 has the formidable proteolytic enzyme activity, it may affect extensive substrates, includes the extracellular matrical all protein components nearly.MMP-13 holds inner status in the remoulding process of extracellular matrix, it not only may degrade the extracellular matrix directly, but also play the role through activating other MMP family members. Under the physiological condition the expression of MMP-13 is only restricted in the remoulding process of skeletal system, but MMP-13 has the expression in many kinds of tumour cells, the expression of MMP-13 has a kind of restrictive characteristic relative to other MMP family members, the overexpression of MMP-13 protein belongs to pathological state and relates with tumour cell's growth, soakage and attack, it affects tumor's development. The anticarcinogen that takes tumor degradation matrix as target prevents tumor's metastasis through suppressing oncocyte attacking the desmohemoblast and penetrating vessel impediment shift. The vital role of MMPs and TIMP in tumour's attack and metastasis process provides an important target to anti-tumor metastasis treatment. Matrix metalloproteinase inhibitor and MMPs hold dynamic balance in vivo, they can maintain ectomatrix degradation balance, when the expression of body MMPs overmuch, matrix metalloproteinase inhibitor will display its function, suppress the overexpression of MMPs.The massive research data indicats that the MMP inhibitor not only can suppress ECM's degradation, but also demonstrates its effect in suppressesing the form of newborn blood vessel, and it can reduce the primary tumor's growth and reduce the quantity and scale of metastatic tumor simultaneously. Therefore, many developed synthetical MMP inhibitors have entered every clinical trial stage ofⅠ-Ⅲterm . They have obtained good effectiveness in the clinical trial, particularly MMPI and the chemotherapy's union use.Experimental purpose:through observe the variation of Chinese materia medica fineleaf schizonepeta herb extraction concentration gradient depressant effect variation to MMPs, investigate Chinese materia medica fineleaf schizonepeta herb extraction depressant effect to MMPs,and indirect confirm the mechanism of action of iatreusis to tumor especially to lung cancer.Experimental principle and method: According to enzyme degradation of fluorescent substrate issued fluorescence principle, We study the inhibitory activity of fineleaf schizonepeta herb to MMP by drug design targeted on MMPs.The determination of inhibiting action is adding the fineleaf schizonepeta herb extractive in the reaction system. Thus,the inhibiting compositions in the extractive cohere with MMP-13 and making the substrate shouldn't cohere with MMP-13, so the velocity of degrading substance lower.Then the status that the extractives of fineleaf schizonepeta herb inhibit MMP-13 by the change of fluorescence intensity is chalked up.The relation of concentration of the fineleaf schizonepeta herb extractive and the velocity of degrading substance is observed by different concentration of the fineleaf schizonepeta herb extractive in different group. The experiments have two groups. One is purification fineleaf schizonepeta herb by chroma- tography and allocation liquor of different concentration. The other is detection changes of fineleaf schizonepeta herb extractive by different concentration inhibit MMP by the method of fluorescent substrate.Experimental result:The experimental result proves,fineleaf schizonepeta herb extractive have inhibitory on MMP-13 activity,and the required amount of fineleaf schizonepeta herb at MMP-13 inhibit the activity of 50% is 18.26mg/ml, namely IC50=18.26mg/ml. The concentration of the fineleaf schizonepeta herb extractive varies directly the velocity of degrading substance. Based on the foundation above, it is concluded that fineleaf schizonepeta herb should inhibit MMPs, which probably is an important mechanism of action that the therapy of tumor by fineleaf schizonepeta herb.The traditional chinese drugs have the advantages that many target, many link and many effect, and its can affect many aspects in tumorigenesis. It has attracted increasing attention. In developping the new drugs on therapy of tumor, the traditional Chinese medicine cannot be ignored. And the therapy of tumor by the traditional Chinese medicine is the key to the study.