| Gastric cancer is a common malignant disease in our country. The investigation of the mechanism on medicine prevention and therapy will provide us with new idea for clinical treatment for gastric neoplasm. Peroxisome proliferaterator-activated receptors( PPARs) are a group of nuclear hormone receptors. While combining with their ligands, PPARs could promote the transcription of target gene in nuclear. PPARs stand on the cross-section of multiple transcriptional signaling pathways, and correlate well with varies of metabolism diseases and cancer. PPARy is a member of PPARs family, with most complicate biological function. To act with the PPRE of target gene, PPARy must form a heterodimer (PPARy /RXRa) by combining with another kind of nuclear hormone receptors superfamily, retinoid X recepor a (RXRa). PPARy expresses in a high level in many kinds of malignant tissue and cell lines, such as liposoma, breast cancer, colorectal cancer and lung cancer. Recently, a new treatment method is directed to ultilize synthesized ligand drugs for either PPARy or RXRa to induce differentiation and apotosis in tumor. The option of traditional chemicaltherapy for malignant tumor is restricted for the side effects. The application of ligands for PPARy and retinoid recepor could offer a high effect and low toxity therapy. In recent years, the relationship of COX-2 and tumors has been paid more and more attention. COX-2 mRNA and protein, but not COX-1, were elevated in colorectal adenocarcinomas, and cancer of the pancreas, lung, prostate and osteogenic sarcoma when compared with normal tissue. Inhibitors of COX, nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit colon, pancreas, breast, and lung from carcinogenesis in experimental animals and humans. Some inhibitors of COX-2 are also the agonists of PPARy. Further study is needed to eluminate the interrelation between the two in carcinogenesis and cancer progression.In this study, we investigate the expression of protein and mRNA of PPARy and RXRa in gastric cancer tissue and cell lines, and the effects of ligands for PPARy and RXRa on the growth and proliferation of gastric cancer cell, and the effects of ligands for PPARy and RXRa on the proliferation, cell cycle, PGs synthesis, and tumorgenesis of gastric cancer transfected with hCOX-2 antisense gene, in order to find the correlation PPARy and COX-2 in gastric cancer.The main contents are summarized as following:1. Immunohistochemical detection suggested that compared with those in chronic gastritis, expressions of PPAR Y and RXRa in gastric mucosal dysplasia and gastric carcinoma were significantly elevated(P<0.05, PO.01). From chronic non-atrophic gastritis, chronic atrophic gastritis to gastric carcinoma, expressions of PPAR Y and RXR a showed an ascending tendency. The expression rates showed no correlation with node metastasisand tendency of differentiation. Expressions of PPAR Y and RXR a correlated significantly, (r =0.54, P<0.01)2. Immunocytochemical method and Western blot showed PPAR Y and RXR a protein expressed in SGC7901, MKN45, MGC803 and AGS gastric cancer cell lines. The ranks for the expression of PPAR Y and RXRcc are MKN45>MGC803>SGC7901>AGS and SGC7901>MKN45>MGC803 >AGS, respectively.3. RT-PCR suggested that the expression of PPARy and RXRa in mRNA level ranked MKN45>SGC7901>AGS>MGC803.4. MTT method showed that the ligands of PPARy and RXRa, 15-d-PGJ2, ciglitazone, BRL49653 and 9-cis-RA, took inhibitory effect on the growth of gastric cancer MKN45 and AGS, in a dose-dependent way(P<0.05, P<0.01). The effect of combining use of ligand drugs was stronger than single dose. BRL49653 showed the strongest inhibitory effect, while 9-cis-RA was much weaker. The extend of drug inhibition correlated well with the expression level of receptor protein.5. H proliferation detection suggested that the inhibitory influence of the former 4 ligands on AS-SGC7901 cell is significantly weaker than SGC7901 cell not transfected with the antisense gene. Therefore, inactivation of COX-... |
PDF Full Text Request