Novel antitumor strategies by targeting to eicosanoid receptor-mediated cellular signaling

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The soluble prostaglandin E_2 receptor(FuEP2/ Ex2) suppressed cancer cell growth and production of hemorrhagic ascites in an orthotopic xenograft model of endometrial cancer and intraperitoneal dissemination model of ovarian cancer. In endometrial cancer, we also revealed that this inhibition was associated with suppression of ERK1/ 2-phosphorylation and COX-2, VEGF, and c-fos mRNA induction, which are consequences of EP receptor-elicited cellular signaling. By using conditional expression system which can be controlled by doxycycline, we obtained stable transfectant of 15-hydroxyprostaglandin dehydrogenase(15-PGDH) derived from human pancreas cancer cell line. We found that expression of 15-PGDH causes decrease of cell growth and survival rate, desensitization to insulin-and epidermal growth factor-induced cell growth, and sensitization to TNF-related apoptosis inducing ligand-induced apoptosis.