Dienogest May Reduce Estradiol- and Inflammatory Cytokine-Induced Cell Viability and Proliferation and Inhibit the Pathogenesis of Endometriosis: A Cell Culture- and Mouse Model-Based Study

• Published in: Biomedicines 2022-11, Vol.10 (11), p.2992
• Main Authors: Kim, Hyun Jin, Kim, Sung Hoon, Oh, Young Sang, Lee, Sa Ra, Chae, Hee Dong
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; AKT protein; Animal models; Cell culture; Cell growth; cell proliferation; Cell viability; Comparative analysis; Computer software industry; Cytokines; dienogest; Endometriosis; Endometrium; Estradiol; Estrogens; GTP-binding protein; Health aspects; IL-1β; Immunohistochemistry; Inflammation; Interleukins; Kinases; Medical research; Membranes; Ovulation; p21-activated kinase; Pathogenesis; Pathophysiology; Patients; Phenols; Phosphorylation; Proliferating cell nuclear antigen; Proteins; Stromal cells; Survival analysis; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10112992

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.