Peroxisome proliferator-activated receptor-γ is essential in the pathogenesis of gastric carcinoma

Abstract

To investigate whether peroxisome proliferator-activated receptor gamma (PPAR-gamma) is expressed in human gastric carcinoma and whether PPAR-gamma is a potential target for gastric carcinoma therapy. PPAR-gamma protein in gastric carcinoma was examined by immunohistochemistry. In the gastric carcinoma cell line MGC803, PPAR-gamma, survivin, Skp2 and p27 protein and mRNA were examined by Western blotting and real-time reverse transcription-polymerase chain reaction, respectively; proliferation was examined by MTT; apoptosis was examined by chromatin staining with Hoechst 33342 and fluorescence activated cell sorting (FACS). and cell cycle was examined by FACS; the knockdown of PPAR-gamma was done by RNA interference. A high level of expression of PPAR-gamma was observed in human gastric carcinoma and in a human gastric carcinoma cell line MGC803. The PPAR-gamma agonist 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) inhibited growth, and induced apoptosis and G(1)/G(0) cell cycle arrest in MGC803 cells in a concentration-dependent and time-dependent manner. The effect of 15d-PGJ(2) on MGC803 cells was not reversed by the selective and irreversible antagonist GW9662 for PPAR-gamma. Furthermore, survivin and Skp2 expression were decreased, whereas p27 expression was enhanced following 15d-PGJ(2) treatment in a dose-dependent manner in MGC803 cells. Interestingly, we also found that small interfering RNA for PPAR-gamma inhibited growth and induced apoptosis in MGC803 cells. The inhibition of PPAR-gamma function may be a potentially important and novel modality for treatment and prevention of gastric carcinoma. A PPAR-gamma agonist inhibited growth of human gastric carcinoma MGC803 cells by inducing apoptosis and G(1)/G(0) cell cycle arrest with the involvement of survivin, Skp2 and p27 and not via PPAR-gamma.