Abstract 3606: The effect of PGE2 receptor inhibitor on the microenviroment of scirrhous gastric cancer
Authors: Fukuoka Tatsunari , Yashiro Masakazu , Takeda Hiroshi , Maruyama Takayuki , Kasashima Hiroaki , Masuda Go , Kinoshita Haruhito , Morisaki Tamami , Sakurai Katsunobu , Shibutani Masatsune , Yamazoe Sadaaki , Kimura Kenjiro , Nagahara Hisashi , Toyokawa Takahiro , Amano Ryosuke , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Otani Hiroshi , Maeda Kiyoshi , Ohira Masaichi , Hirakawa Kosei 
Published: May 2015

Introduction: Prostaglandins and cyclooxygenase2 have been suggested to play an important role for the proliferation and migration of cancer cells. But Prostaglandins (PG) have been suggested to affect cancer cells in various directions. For example, PGF2α and PGD2 has been demonstrated to have anti-tumor effects against some types of cancer cells. But PGE2 has been demonstrated to promote the proliferation and migration of cancer. Therefore, the investigation of the involvement of PG signals for cancer in lower level of arachidonic acid cascade is very important. The aim of this study is to investigate the effects of PGE2 and PGE2 receptor inhibitor (EP2 inhibitor) on the growth-interaction between cancer cells and fibroblasts.

Methods: Three human gastric cancer cell lines (OCUM-2M, OCUM-2MD3, OCUM-12) and a human gastric fibroblast (CAF45) cell line were used in this study. Serum-free conditioned medium (SF-CM) from CAF-45 stimulated with PGE2 or EP2 inhibitor was prepared and used in study. Cell proliferation was studied by MTT assay and cell count in the presence or absence of CAF45. Cell migration was studied by wound healing assay in the presense or absence of SF-CM. In vivo study, We examined the effect of EP2 inhibitor on subcutaneous and orthotopically transplanted tumors.

Results: In proliferation, PGE2 significantly stimulated the proliferation and migration of cancer cells. PGE2 significantly stimulated the proliferation and migration of cancer cells co-cultured with CAF45 or SF-CM more in comparison with single culture. EP2 inhibitor significantly decreased the proliferation and migration of cancer cells, EP2 inhibitor significantly decreased the proliferation migration of cancer cells co-cultured with CAF-45 or SF-CM more in comparison with single culture. In vivo study, EP2 inhibitor significantly suppressed the subcutaneous tumor in nude mice and suppressed orthotopic tumor growth and lymph node metastasis.

Conclusion: PGE2 is associated with progression of gastric cancer. PGE2 receptor inhibitors might be promising anti-cancer drug for gastric carcinoma.

Citation Format: Tatsunari Fukuoka, Masakazu Yashiro, Hiroshi Takeda, Takayuki Maruyama, Hiroaki Kasashima, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Katsunobu Sakurai, Masatsune Shibutani, Sadaaki Yamazoe, Kenjiro Kimura, Hisashi Nagahara, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. The effect of PGE2 receptor inhibitor on the microenviroment of scirrhous gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3606. doi:10.1158/1538-7445.AM2014-3606