Study On The Inhibitory Effect Of Pyrogallic Acid On Matrix Metalloproteinases And Anti-tumor Activity

The typical characteristics of malignant cells are constantly invasion surrounding tissue, form metastases in a distant organ. The tumor invasion and metastasis are important reason for the death of patients. Accordingly, tumor invasion and metastasis mechanism is a hot topic. Tumor metastasis is a multi-stage and complex processes with interaction process between the tumor cells and extracellular matrix (ECM), there are three main steps: adhesion, degradation, migration. Matrix Metalloproteinases (MMPs) is the most important enzyme for degradation the extracellular matrix.MMPs are a class of zinc metalloproteinases that degrade ECM components and play important roles in development, morphogenesis, and a variety of pathological conditions, such as cardiovascular diseases, cancer, inflammation, et al. So, as a therapeutic target, to designing and searching the selectivity MMP inhibitor is very popular in cancer therapy area recent years.This paper mainly has done the following work:1 To DQ-Gelatin as substrate, MMP degradation the substrate that can generate fluorescence peptides. And we measured the activity By measuring fluorescence intensity.2 Cell model can choose a variety of secreted MMPs the fibro sarcoma cells (HT1080), cell adhesion experiments using camera and microscope observation of blood cell count after count the amount; cell extending experiments were used the two-dimensional culture and the three-dimensional culture in collagenâ… , cell migration experiments using crossed detected.3 Animal experiments carried out on the C57BL/6 mice of melanoma tumor affected, as well as the PA effect in vivo metastasize studies in C57BL / 6 mice.By the following conclusions:1 PA has inhibitory activity of MMPs, particular on MMP-7, on the membrane-type MMP-14 and MMP-16 the inhibitory effect is not good. PA to certain MMPs have a stronger effect, the type of inhibition is competitive form or competition-oriented hybrid form.2 Cytology experiments show that the PA inhibit the extension in the two-dimensional and three-dimensional state especially in the three-dimensional, and at the same time, inhibit the migration of these cells.3 The PA inhibited injection of Lewis lung carcinoma growth and the inhibition rate was 67% (P <0.001).And the PA inhibited the metastasize of B16-F10 cells in vivo.4 In Acute toxicity test, the LD50 for the PA was 862.2982 mg / kg body weight. This paper judged it as a low-toxicity compounds, and shew that PA has the anti-tumor potential.