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P rostaglandin d synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ
Author(s) -
Fukuoka Tatsunari,
Yashiro Masakazu,
Kinoshita Haruhito,
Morisaki Tamami,
Hasegawa Tsuyoshi,
Hirakawa Toshiki,
Aomatsu Naoki,
Takeda Hiroshi,
Maruyama Takayuki,
Hirakawa Kosei
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29392
Subject(s) - prostaglandin , cancer research , medicine , pharmacology , biology
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 γ (PPARγ) were evaluated by RT‐PCR. The effects of a PPARγ antagonist or siPPARγ 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. PPARγ 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 PPARγ. PGDS increased the PGD 2 production of gastric cancer cells. A PPARγ antagonist and siPPARγ 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 PPARγ 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 PPARγ signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPARγ.