Prostaglandin D Synthase Is A Potential Novel Therapeutic Agent For The Treatment Of Gastric Carcinomas Expressing Ppar Gamma

The antitumor activity of prostaglandin (PG) D-2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD(2) is not useful from a clinical point of view because it is rapidly metabolized in vivo. The aim of this study was to clarify the antitumor efficacy of an alternative, PGD synthase (PGDS), on gastric cancer cells. The effects of PGD(2) and PGDS on the proliferation of gastric cancer cells were examined in vivo and in vitro. The expression levels of PGD(2) receptors and peroxisome proliferator-activated receptor (PPAR) were evaluated by RT-PCR. The effects of a PPAR antagonist or siPPAR on the proliferation of cancer cells and the c-myc and cyclin D1 expression were examined in the presence or absence of PGD(2) or PGDS. PPAR was expressed in gastric cancer cell lines, but PGD(2) receptors were not. PGD(2) and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPAR. PGDS increased the PGD(2) production of gastric cancer cells. A PPAR antagonist and siPPAR transfection significantly suppressed the growth-inhibitory effects of PGD(2) and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD(2); this inhibitory effect was suppressed by PPAR antagonist. Both PGD(2) and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than PGD(2) treatment. These findings suggest that PGDS and PGD(2) decrease the proliferation of gastric cancer cells through PPAR signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPAR.What's new? Previous work suggests that prostaglandin D-2 (PGD(2)) exerts antiproliferative effects in certain types of cancer cells. But because PGD(2) is rapidly catalyzed to its inactive form, its clinical utility is limited. A possible alternative to PGD(2) is PGD synthase (PGDS), which synthesizes PGD2, but whether it also possesses antitumor activity is unknown. In this study, in PPAR-expressing gastric cancer cells, both PGD(2) and PGDS were found to significantly suppress cell proliferation. In vivo, they inhibited the growth of subcutaneous tumors. Tumor volume was markedly decreased with PGDS treatment, compared with PGD(2).