Background & Aims: The antitumor activity of prostaglandin (PG) D2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD2 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, PGD2 synthase (PGDS), on gastric cancer cells. This is the first report showing that PG synthase is a promising agent for the treatment of gastric carcinomas that express peroxisome proliferator-activated receptor γ (PPARγ).

Methods: The effects of PGD2 and PGDS on the proliferation of gastric cancer were examined in vivo and in vitro for five human gastric cancer cell lines. The expression levels of PGD2 receptors and PPARγ were evaluated by RT-PCR. The effects of PGD2 and PGDS on the expression of c-myc and cyclin D1 were examined by Western blotting in the presence or absence of a PPARγ antagonist.

Results: PPARγ was expressed in gastric cancer cell lines, but PGD2 receptors were not. PGD2 and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPARγ. PGDS increased the PGD2 production of gastric cancer cells. A PPARγ antagonist significantly suppressed the growth-inhibitory effects of PGD2 and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD2; this inhibitory effect was suppressed by the PPARγ antagonist. Both PGD2 and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than after PGD2 treatment. PGD2 decreased the proliferation of gastric cancer cells through PPARγ signaling.

Conclusion: PGDS and PGD2 decreased the proliferation of gastric cancer via the PPARγ pathway. PGDS is a promising therapeutic agent for gastric cancer and PPARγ might be a predictive biomarker for PGDS treatment in gastric cancer.

Citation Format: Masakazu Yashiro, Tatsunari Fukuoka, Haruhito Kinoshita, Go Masuda, Kishu Kitayama, Yuichiro Miki, Tamami Morisaki, Tsuyoshi Hasegawa, Kosei Hirakawa. Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1281.