Expression Of Skp2, Heparanase, NF-κB And PPARγ In Gastric Carcinoma And Effect Of 15d-PGJ₂ And RNA Interference Silencing PPARγ On Growth Of Human Gastric Carcinoma Cells And Its Mechanism

Objectives: Gastric carcinoma is one of the most common malignant tumors. Its prognosis is poor, therapy is very difficult and mortality is enormous high. Therefore, it is extremely important to investigate pathogenesis and search new target of prevention and therapy and effective drug in gastric carcinoma for decreased morbidity and mortality, increased survival rate and prolonged life span of gastric carcinoma patients.S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin- dependent kinase inhibitor p27. Some research have shown that Skp2 overexpression has been implicated in cell transformation and oncogenesis, and tumor suppressor protein PTEN may regulate ubiquitin-mediated p27 proteolysis through regulating Skp2. Skp2 may provide a new target for anticancer therapy drugs inhibiting cell cycle proceeding.Heparanase (HPA) is the only endoglycosidase in mammal cell so far that degrades heparan sulfate in extracellular matrix and basement membrane. HPA plays a central role in inflammation, angiogenesis and invasiveness and metastasis of diverse malignant tumors. Perhaps it is a new target for anticancer therapy. NF-κB is a dimeric transcription factor that is involved in the regulation of genes associated with inflammation and apoptosis. Recent studies have shown that NF-κB is also a transcriptional factor of matrix metalloproteinases 9 (MMP9) and urokinase plasminogen activator (uPA) and plays a role in the metastatic process of malignant tumor. Recent studies in vitro have shown that NF-κB also regulated HPA expression.Peroxisome proliferators-activated receptorγ(PPARγ) that belongs to the...