Abstract 3995: Antitumor effect of prostaglandin D2 by peroxisome proliferator-activated receptor gamma (PPARγ)-dependent pathway in gastric carcinoma.
Authors: Tatsunari Fukuoka, Masakazu Yashiro, Hiroshi Takeda, Takayuki Maruyama, Haruhito Kinoshita, Tamammi Morisaki, Tsuyoshi Hasegawa, Toshiki Hirakawa, Naoki Aomatsu, Katsunobu Sakurai, Kenjiro Kimura, Hisashi Nagahara, Takahiro Toyokawa, Ryosuke Amano, Eiji Noda, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2013)

Abstract Introduction: Prostaglandin D2 (PGD2) has been demonstrated to have not only physiological responses but also anti-tumor effects against some types of cancer cells such as a lung cancer. PGD2 act through two major receptors, DP1 and DP2 of chemoattractant receptor-like molecule on the Th2 cell. Recently, some papers reported that PGD2 may act through PPARγ, suggesting that the effects of PGD2 are involved in either PGD2 dependent or independent pathway. PGD2 metabolite, 15-deoxy-Δ12 14-PGJ2, activates peroxisome proliferator-activated receptor γ (PPARγ) which induces growth inhibition of various cells. PPARγ is expressed in various types of cancers including gastric cancer. Since the role of PGD2 on gastric cancer cells is still unknown, this study is aimed to investigate the effect of PGD2 signalings on the proliferation of gastric cancer cells. Materials and Methods: Three human gastric cancer cell lines, OCUM-2M, OCUM-12, and MKN-74, were used. Effect of PGD2 or PPARγ antagonist on the proliferation of cancer cells was examined by MTT assay. The expression level of PGD2 receptor, DP1 and DP2, and PPARγ of gastric cancer cells was examined by RT-PCR. The effect of PGD2 on cell cycle was examined with PI staining by flowcytometry. Results: PGD2 significantly decreased the proliferation of OCUM-2M and MKN-74 cells at a dose-dependent manner, but not that of OCUM-12. PGD2 receptors, DP1 and DP2, were not expressed in 3 gastric cancer cell lines while PPARγ was expressed in OCUM-2M and MKN-74. BADGE, a PPARγ antagonist, significantly suppressed the growth-inhibitory effects of PGD2 on OCUM-2M and MKN-74 cells. PGD2 increased G0/G1 phase of cancer and decereased G2/M phase. Conclusion: PGD2 decreased the proliferation of gastric cancer cells through PPARγ dependent pathway. PGD2 might be a promising therapeutic agent for gastric cancer with PPARγ expression. Citation Format: Tatsunari Fukuoka, Masakazu Yashiro, Hiroshi Takeda, Takayuki Maruyama, Haruhito Kinoshita, Tamammi Morisaki, Tsuyoshi Hasegawa, Toshiki Hirakawa, Naoki Aomatsu, Katsunobu Sakurai, Kenjiro Kimura, Hisashi Nagahara, Takahiro Toyokawa, Ryosuke Amano, Eiji Noda, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Antitumor effect of prostaglandin D2 by peroxisome proliferator-activated receptor gamma (PPARγ)-dependent pathway in gastric carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3995. doi:10.1158/1538-7445.AM2013-3995