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

可溶性前列腺素E_2受体（FuEP 2/Ex 2）抑制子宫内膜癌原位移植模型和卵巢癌腹腔内转移模型中癌细胞的生长和出血性腹水的产生。在子宫内膜癌中，我们还发现这种抑制与ERK 1/ 2磷酸化和考克斯-2、VEGF和c-fos mRNA诱导的抑制有关，这些都是EP受体引起的细胞信号传导的结果。利用强力霉素调控的条件表达系统，从人胰腺癌细胞系中获得了15-羟基前列腺素脱氢酶（15-PGDH）的稳定转染子。我们发现，15-PGDH的表达导致细胞生长和存活率下降，对胰岛素和表皮生长因子诱导的细胞生长脱敏，并对TNF相关的凋亡诱导配体诱导的凋亡敏感。

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.