Saito Fumitaka, Tashiro Hironori, Yamaguchi Munekage, Honda Ritsuo, Ohba Takashi, Suzuki Akira, Katabuchi Hidetaka
a Department of Obstetrics and Gynecology , Faculty of Life Sciences, Kumamoto University , Kumamoto , Japan and.
b Division of Cancer Genetics , Medical Institute of Bioregulation, Kyushu University , Fukuoka , Japan.
Gynecol Endocrinol. 2016;32(5):403-7. doi: 10.3109/09513590.2015.1124411. Epub 2015 Dec 18.
As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma.
METHODS/MATERIALS: Pten(loxP/loxP) mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed.
Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment.
Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms.
随着子宫内膜癌年轻女性患者数量的增加，保留生育功能的治疗受到了更多关注。尽管已有多篇关于孕激素保守治疗子宫内膜癌的报道，但在日本仅有醋酸甲羟孕酮（MPA）可用。地诺孕素已被开发为治疗子宫内膜异位症的第四代孕激素。由于其高孕激素活性，其抗肿瘤活性引起了关注。在本研究中，我们使用子宫内膜癌小鼠模型研究了地诺孕素对子宫内膜肿瘤的抗癌作用。
方法/材料：给Pten(loxP/loxP)小鼠皮下注射MPA或地诺孕素，以评估其对小鼠发生的子宫内膜肿瘤的抗癌效果。注射一周后进行组织病理学分析。
在接受地诺孕素或MPA治疗的每组八只小鼠中，各有一只（12.5%）发现了子宫内膜肿瘤。相比之下，在未接受孕激素治疗的八只小鼠中有七只（87.5%）发现了肿瘤。与未治疗的小鼠相比，每种孕激素治疗对小鼠发生的子宫内膜肿瘤均显示出抗癌活性。
在地诺孕素和MPA在我们的小鼠模型中对子宫内膜肿瘤显示出强大的抗癌活性。本研究表明，地诺孕素可能是治疗人类子宫内膜肿瘤的一种有用药物。
