The Effect of Rosiglitazone on the Cell Proliferation and the Expressions of p27 and Skp2 in Helicobacter pylori Infected Human Gastric Epithelial Cells / 대한소화기학회지

ABSTRACT

BACKGROUND/AIMS: Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the ligand-activated nuclear receptor superfamily, exhibit anti-tumoral effects and are associated with de novo synthesis of proteins involved in regulating the cell cycle and cell survival/death. Helicobacter pylori (H. pylori) is an etiologic agent for gastric adenocarcinoma, and raises the cell turnover of gastric epithelium. The aim of this study was to investigate the effect of PPAR gamma ligand rosiglitazone on the cell proliferation and the expressions of p27 and Skp2 protein in H. pylori infected gastric epithelial cells. METHODS: We examined the expression of PPAR gamma by Western blot in H. pylori infected AGS human gastric epithelial cells. The effect of rosiglitazone on the survival of H. pylori infected AGS cells was assessed by cell viability assay. After the treatment of rosiglitazone in H. pylori infected AGS cells, the expressions of p27 and Skp2 were assessed by Western blot. RESULTS: The expression of PPAR gamma protein was increased in H. pylori infected AGS cells. Cell growth was inhibited and decreased in dose- and time- dependent manner in H. pylori infected AGS cells treated with rosiglitazone. A decrease in Skp2 expression and a reciprocal increase in p27 expression were found in dose- and time-dependent manner in H. pylori infected AGS cells treated with rosiglitazone. CONCLUSIONS: Rosiglitazone inhibited the growth of H. pylori infected AGS cells. Rosiglitazone attenuated Skp2 expression, thereby promoting p27 accumulation in H. pylori infected human gastric epithelial cells. Further studies will be needed to find the effects of accumulation on cell turnover in H. pylori infection and the role in the H. pylori-associated gastric carcinogenesis.