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Published on: February 26, 2019
Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial
Fumitaka Saito1, Hironori Tashiro1, Munekage Yamaguchi1
1a Department of Obstetrics and Gynecology , Faculty of Life Sciences, Kumamoto University , Kumamoto , Japan and.
Objective:
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.
Results:
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.
Conclusions:
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.
Insights
Dienogest and medroxyprogesterone acetate (MPA) demonstrated significant anticancer effects against endometrial neoplasms in a mouse model. This suggests dienogest may be a viable fertility-sparing treatment option for endometrial cancer.
Area of Science:
- Gynecology
- Oncology
- Pharmacology
Background:
- Endometrial carcinoma incidence is rising in younger women, increasing the need for fertility-sparing treatments.
- Medroxyprogesterone acetate (MPA) is a progestin used for endometrial cancer, but dienogest, a potent fourth-generation progestin, shows promise.
- Dienogest's high progesterone activity has led to investigations into its potential antitumor effects.
Purpose of the Study:
- To evaluate the anticancer efficacy of dienogest compared to MPA in a mouse model of endometrial carcinoma.
- To assess the potential of dienogest as a fertility-sparing therapeutic agent for endometrial neoplasms.
Main Methods:
- A mouse model of endometrial carcinoma was utilized.
- Mice with developed endometrial neoplasms were subcutaneously injected with either dienogest or MPA.
- Histopathological analyses were conducted one week post-injection to evaluate treatment effects.
Main Results:
- Dienogest and MPA treatments significantly reduced the incidence of endometrial neoplasms.
- Only 12.5% of mice treated with dienogest or MPA developed neoplasms, compared to 87.5% in the untreated group.
- Both progestins exhibited notable anticancer activity against endometrial neoplasms in the mouse model.
Conclusions:
- Dienogest and MPA exhibited potent anticancer activity in the studied mouse model of endometrial neoplasms.
- The findings suggest that dienogest could serve as a valuable therapeutic agent for human endometrial neoplasms.
- Dienogest warrants further investigation as a potential fertility-sparing treatment for endometrial cancer.
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