Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Sci Rep. 2021 Oct 13;11(1):20279. doi: 10.1038/s41598-021-99694-y.
Prostaglandin E2 plays an important role in carcinogenesis and malignant potential of prostate cancer (PC) cells by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of the EP receptor antagonist are unclear. In this study, we used a mouse model of PC. The mice were provided standard feed (control) or feed containing the EP1 receptor antagonist and were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using a cleaved caspase-3 assay. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. These findings indicate that feeding with the addition of EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that the EP1 receptor antagonist may be a novel chemopreventive agent for PC.
前列腺素 E2 通过与其特定受体 E 型前列腺素（EP）受体结合，在前列腺癌（PC）细胞的癌变和恶性潜能中发挥重要作用。然而，EP 受体拮抗剂的抗癌作用尚不清楚。在本研究中，我们使用了一种 PC 小鼠模型。这些小鼠提供标准饲料（对照组）或含有 EP1 受体拮抗剂的饲料，并在 10、15、30 和 52 周龄时处死。通过使用 cleaved caspase-3 测定法进行免疫组织化学分析来评估细胞凋亡。在 15、30 和 52 周龄时，实验组的癌症发病率明显低于对照组。在 30 和 52 周龄时，实验组中分化不良的 PC 细胞的百分比明显低于对照组。实验组中细胞凋亡的百分比明显高于对照组在 15、30 和 52 周龄时。这些发现表明，通过上调细胞凋亡，添加 EP1 受体拮抗剂的饮食可延迟 PC 的进展。我们建议 EP1 受体拮抗剂可能是一种新型的 PC 化学预防剂。
