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Geburtshilfe Frauenheilkd 2017; 77(01): 66-72
DOI: 10.1055/s-0042-115566
GebFra Science
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat Study

Der mTOR-Inhibitor Everolimus verringert endometriotische Krankheitsherde: Eine experimentelle Studie an der Ratte
T. Kacan
1   Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
,
C. Yildiz
2   Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey
,
S. Baloglu Kacan
3   Department of Internal Medicine, Sivas Numune Hospital, Sivas, Turkey
,
M. Seker
1   Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
,
H. Ozer
4   Department of Pathology, Cumhuriyet University School of Medicine, Sivas, Turkey
,
A. Cetin
2   Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey
› Author Affiliations
Further Information

Publication History

received 09 June 2016
revised 28 July 2016

accepted 17 August 2016

Publication Date:
30 January 2017 (online)

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Comment on:

mTor Inhibitors for the Treatment of EndometriosisGeburtshilfe Frauenheilkd 2018; 78(03): 283-284
DOI: 10.1055/s-0043-124518

Abstract

Introduction Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model.

Materials and Methods Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5 mg/kg/day, p. o.), anastrozole (0.004 mg/day, p. o.), or normal saline (0.1 mL, i. p.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax.

Results Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment.

Conclusion Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.

Zusammenfassung

Einleitung Mammalian Target of Rapamycin (mTOR, deutsch: Ziel des Rapamycins im Säugetier) funktioniert als Signalweg zur Verhinderung von Apoptose. Neue Studien haben gezeigt, dass die Aktivität des mTOR-Signalwegs in endometriotischen Läsionen erhöht ist. Ziel dieser Studie war es, die Auswirkungen von Everolimus, einem Rapamycin-Analogon, in einem experimentellen Endometriosemodell zu studieren.

Material und Methoden Es wurde eine Endometriose durch Autotransplantation von Gebärmuttergewebe in die Bauchhöhle von 24 Ratten hervorgerufen. Das Vorhandensein der Endometriose wurde anschließend überprüft. Die Tiere wurden danach in 3 Gruppen randomisiert und erhielten über 14 Tage hinweg entweder Everolimus (1,5 mg/kg/d, p. o.), Anastrozol (0,004 mg/d, p. o.), oder Kochsalzlösung (0,1 mL, i. p.). Endometriotische Krankheitsherde wurden operativ entfernt, mit Hämatoxylin und Eosin eingefärbt, und das Ausmaß der Endometriose wurde semiquantitativ bewertet. Zusätzlich wurde eine immunhistochemische Analyse mit Primärantikörper von Vascular Endothelial Growth Factor, CD117 und Bax durchgeführt.

Ergebnisse Die Gabe von Anastrozol wie auch von Everolimus verringerte die Endometriosewerte. Nach der Behandlung mit Anastrozol wurde aber ein signifikanter Rückgang ovarieller Follikel vermerkt, der nach einer Behandlung mit Everolimus nicht auftrat.

Schlussfolgerung Die Apoptose-fördernde Wirkung von Everolimus verringerte die endometriotischen Krankheitsherde, ohne dass die ovarielle Reserve negativ beeinflusst wurde. Dieses Ergebnis stützt die Vermutung, dass weitere Studien zur Wirksamkeit von Everolimus als potenzielles Medikament gegen Endometriose nötig sind.

Key words

apoptosis - endometriosis - everolimus - ovarian reserve

Schlüsselwörter

Apoptose - Endometriose - Everolimus - ovarielle Reserve
 

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