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Dienogest attenuates STAT3 activation in ovarian endometriotic cysts
JongYeob Choi1, MinWha Jo2, EunYoung Lee1
1Infertility Clinic, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
Objective:
Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation.
Study Design:
STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation.
Result:
STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs.
Conclusion:
Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.
Insights
Dienogest treatment reduces excessive signal transducer and activator of transcription 3 (STAT3) activation in endometriosis. This inhibition impacts cell proliferation, invasion, and apoptosis, offering a potential therapeutic pathway for endometriosis.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Cellular mechanisms in gynecological diseases
Background:
- Endometriosis is linked to overactive signal transducer and activator of transcription 3 (STAT3) signaling.
- STAT3 regulates key cellular processes including proliferation, invasion, and apoptosis.
- Targeting STAT3 activation may be a therapeutic strategy for endometriosis.
Purpose of the Study:
- To investigate if dienogest's anti-endometriotic effects are mediated by regulating STAT3 activation.
- To assess the impact of dienogest on STAT3 signaling in endometriosis.
Main Methods:
- Evaluated STAT3 activation in normal endometrial and endometriotic tissues from patients with/without dienogest treatment.
- Conducted in vitro studies using endometriotic cyst stromal cells (ECSCs) to confirm dienogest's direct effect on STAT3 activation.
- Assessed protein expression of PCNA, MMP-2, and BCL-2.
Main Results:
- STAT3 activation was significantly higher in untreated endometriotic tissues compared to normal tissues.
- Preoperative dienogest administration reversed elevated STAT3 activation.
- Dienogest inhibited IL-6-stimulated STAT3 activation in ECSCs, reducing PCNA, MMP-2, and BCL-2 expression.
Conclusions:
- Dienogest effectively inhibits STAT3 activation in endometriotic cyst stromal cells.
- This inhibition influences cellular proliferation, invasiveness, and apoptosis in endometriosis.
- Dienogest's mechanism of action involves the modulation of STAT3 signaling pathways.
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