Prostaglandin d synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ. Issue 5 (8th January 2015)

• Record Type: Journal Article
• Authors: Fukuoka, Tatsunari; Yashiro, Masakazu; Kinoshita, Haruhito; Morisaki, Tamami; Hasegawa, Tsuyoshi; Hirakawa, Toshiki; Aomatsu, Naoki; Takeda, Hiroshi; Maruyama, Takayuki; Hirakawa, Kosei
• Is Part Of: International journal of cancer. Volume 137:Issue 5(2015:Sep. 01)
• Page Start: 1235
• Page End: 1244
• Publication Date: 2015-01-08
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29392
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The antitumor activity of prostaglandin (PG) D<sub>2</sub> has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD<sub>2</sub> is not useful from a clinical point of view because it is rapidly metabolized <italic>in vivo</italic>. 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<sub>2</sub> and PGDS on the proliferation of gastric cancer cells were examined <italic>in vivo</italic> and <italic>in vitro</italic>. The expression levels of PGD<sub>2</sub> receptors and peroxisome proliferator‐activated receptor γ (PPARγ) were evaluated by RT‐PCR. The effects of a PPARγ antagonist or <italic>siPPARγ</italic> on the proliferation of cancer cells and the c‐myc and cyclin D1 expression were examined in the presence or absence of PGD<sub>2</sub> or PGDS. PPARγ was expressed in gastric cancer cell lines, but PGD<sub>2</sub> receptors were not. PGD<sub>2</sub> and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPARγ. PGDS increased the PGD<sub>2</sub> production of gastric cancer cells. A PPARγ antagonist and <italic>siPPARγ</italic> transfection significantly suppressed the growth‐inhibitory effects of PGD<sub>2</sub> and PGDS. Expression of c‐myc and cyclin D1 was significantly decreased by PGD<sub>2</sub>; this inhibitory effect was suppressed by PPARγ antagonist. Both PGD<sub>2</sub> and PGDS significantly decreased subcutaneous tumor growth <italic>in vivo</italic>. Tumor volume after PGDS treatment was significantly less than PGD<sub>2</sub> treatment. These findings suggest that PGDS and PGD<sub>2</sub> decrease the proliferation of gastric cancer cells through PPARγ signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPARγ.</p> </abstract>