Abstract
Dienogest (DNG) is a therapeutic medication used in endometriosis treatment. Limited data are available regarding its mechanism of action on endometrial cells. Using in vivo and in vitro models, we investigated whether DNG treatment causes significant biological changes in human endometrial stromal cells (ESCs). The markers related to the pathogenesis of endometriosis in ESCs were evaluated using estradiol, tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and IL-32, administered alone or in combination with DNG. Implanted endometrial tissues were compared between C57BL/6 mice that did or did not receive DNG treatment by using size measurements and immunohistochemistry. A significant decrease in cell viability, protein kinase B (AKT) phosphorylation, and the expression of p21-activated kinase 4 and vascular endothelial growth factor were observed in ESCs treated with estradiol plus DNG. Cell viability, AKT phosphorylation, and proliferating cell nuclear antigen (PCNA) expression also decreased significantly after TNF-α plus DNG treatment. Treatment with IL-1β or IL-32 plus DNG significantly decreased cell viability or PCNA expression, respectively. The size of the implanted endometrial tissue significantly decreased in mice treated with DNG, accompanied by decreased PCNA expression. Thus, DNG may reduce cell viability and proliferation induced by estradiol, TNF-α, IL-1β, and IL-32, and inhibit the endometriosis pathogenesis by decreasing PCNA expression.