The Effect Of Peroxisome Proliferators Activated Receptor(PPAR)γ Ligand On Proliferation Of Gastric Carcinoma Cell Line MKN45

OBJECTIVES: To investigate the significance of expression of PPARγ in chronic gastritis,gastric mucosal dysplasia and gastric carcinoma.We report peroxisome proliferators activated receptor(PPAR)γ is expressed in human gastric cancer cell line-MKN45 and the effect of PPARγ ligand on proliferation of gastric carcinoma cell line.PPARγ activation changes c-myc gene expression and induce apoptosis of MKN-45 cells.Methods Avidin-biotin peroxidase complex immunohistochemical methods were adopted to examine the expression of PPARγ in patients with chronic gastritis,gastric mucosal dysplasia and gastric carcinoma.We used reverse transcripition-polymerase chain reaction to demonstrate PPARγ expression in MKN45 cell line.PPARγ agonist(Pioglitazone and Rosiglitazone) showed dose-related inhibitory effects on the proliferation of the gastric cancer cells.Pioglitazone and Rosiglitazone can also reduce c-myc gene expression in MKN45 cells.Flow cytometry was adopted to demonstrat cell cycle and apoptosis of MKN-45 cells after treatment with Pioglitazone and Rosiglitazone.Results The positive rates of PPARγ were 47.2% in gastric carcinoma ,26.7%in gastric mucosal dysplasia,15.0%in intestine metaplasia,6.7%in chronic atrophic gastritis.Compared with those in chronic gastritis,expression of PPARγ in gatric mucosal dysplasia and gastric carcinoma were significantly enhanced(P<0.05).PPARγ is expressed in human gastric cancer cell-MKN45.PPARγ agonists (Rosiglitazone and Pioglitazone) showed dose-related inhibitory effects on human gastric cancer cell line MKN-45.PPARγ agonists can also reduce c-myc gene expression in MKN45 cells.Fliw cytometry demonstrated G1 cell cycle arrest and apoptosis of cell after treatment with Rosiglitazone and Pioglitazone.Conclusion PPARγ protein overexpression is a relatively early event in gastric carcinogenesis, induction of apoptosis and decrease of c-myc gene may be the mechanisms of the antiproliferative effect of PPARγ activation in human gastric cancer cell MKN-45.