Effect Of PPARγ Ligand On The Invasion And The Metastasis In Gastric Cancer

Tumor cell extends to far location by invasion and metastasis is main dead reason of gastric cancer patient . Clinic statistics indicates that about 80% tumor patient dead with tumor invasion and metastasis. The invasion and the metastasis of gastric cancer is complex process of multiple step genesis and multiple factor participate in. Among the total, metastasis related gene activation,metastasis inhibiting gene inactivation and controlling gene disturbance are main reason of gastric cancer invasion and metastasis. Therefore investigate correlation factor of gastric cancer invasion and metastasis, to aim directly at certain component element exert an influence, possible to become new strategy of gastric cancer therapy. At present, to aim directly at gastric cancer treatment there is chief operation,radio - therapy, chemotherapy and biotherapy, however, the recurrence of the operation higher than, and side effect of chemotherapy is fairly serious. Accordingly, the intervention of specificity regulating factor to become new direction of tumor therapy.With development of molecular biology and cell biology, the increasing drug target discovered one after another. Peroxisome proliferation activated receptor (PPARs) belong to nucleus hormone receptor superfamily new member . It was discovered by the United Kingdom scientist Issemann et al firstly at 1990 year. The most early discovered that express of PPARs main in adipose tissue, participate in regulation fat metabolism. PPARs is an ligand activated transcription factor,it binds with specific DNA response element,then controls gene express. Maim function of PPARs is transform an various kinds of change of the homeostasis, drugs, nutrition and inflamed stimulus et al to cell signal. PPARs educe an important role of the messenger in the regulation of energy metabolism,the cell differentiation, the proliferation, Apoptosis, Inflammatory reaction, endogenous active compound the synthesis and the secretion. In PPARs the super-family, PPAR7 is the most complicated of biological function and investigate most. PPAR7 is nuclear factor that depends on ligand,its ligand includes natural ligand: 15d - PGJ -2;as well as synthetic ligand:Antidiabetic,for instance Ros-iglitazone and Troglitazone, due to its ligands have high performance, higt selectivity and asepsis, as wel evident depressant effect on tumor cell of expressed PPAR-y. in recent years,the ligand of PPAR7 is new target of investigate tumor the therapy.Sato et al reported that there is the express of PPAR-ymRNA and coding protein in gastric cancer cell, well - differentiated, moderately differentiated, poorly differentiated adenocarcinoma and gastric mucosa with intestinalisation. Liping Yao et al reported that the express of PPAR7 in the gastric mucosa with atypical hyperplasia higher than chronic gastritis significantly, and the express of PPAR-y increases with enhancement of degree of dysplasia in the gastric mucosa , the express of PPAR7 increases in poorly differentiated and gastric cancer with lymph node metastasis, which indicate that the express of PPAR7 is the molecular mark possibly from chronic gastritis to atypical hyperplasia of the gastric mucosa even to gastric cancer, therefore supposed that the express of PPAR7 can relate with the degree of malignancy of tumor.Because the side effect of chemotherapy of malignant tumor is fairly serious, its application was limited, for this reason investigate deeply relationship between PPAR*y and gastric cancer, to applicate PPAR-y ligand to clinical treatment of tumor and to come true treat tumor with high performance, high selectivity and asepsis drug provide valuable scientific data and theory. We will research the effect of PPAR7 ligand on invasion and metastasis of gastric cancer cell , and investigate relationship of PPAR7 ligand with gastric cancer.ObjectiveTo study the express of PPAR7 in human gastric cancer cell line MGC -803;To research effect of PPAR-y activator 15 - d - PGJ -2. Troglitazone onproliferation, adhesion, invasion and metastasis. To investigate initially PPAR-y activator inhibit the mechanism of the tumor proliferation. To search for PPAR-y ligand applicate to clinical treatment of gastric cancer and provide several rationale and experiment foundation.MethodBy Immunofluorescence cytochemistry method detect the express of PPAR-y in gastric cancer cell line MGC - 803, By MTT chromatometry detect effct of different density 15 - d - PGJ - 2 and Troglitazone on proliferation activity and adherion of gastric cancer cell. By invasion system in vitro detect effect of different ligand on invasion and metastasis of gastric cancer cell MGC - 803.ResultThe express Of PPAR7 is located mainly in cell nucleus;15 - d - PGJ -2 and Troglitazone inhibited the proliferation of gastric cancer cell, decreased cell adhesion, locomotory capacity and invasioness to matrigel, to compare with control group have statistical significance, with increasing of ligand density and extension of action time the proliferation of gastric cancer cell decreasing gradually , have time and dose - dependent relationship. The effect of Combination two ligand outweigh one ligand alone.ConclusionHuman gastric cancer cell line MGC - 803 express PPAR7 protein functionality;alone and combination of 15 - d - PGJ -2 and Troglitazone inhibit adhesion and invasion of MGC - 803 cell on ECM at different degree, the effect of combination of two ligand is evident;its mechanism of action need further investigate.