Endocannabinoids modulate apoptosis in endometriosis and adenomyosis
Bilgic et al.·Acta HistochemicaImpact 1.7
UnklarGRADESehr niedrig66 Zitate
StichprobePräklinisch
KontrolleNormales Endometrium/Myometrium
EndpunktApoptotischer Zellindex
Verblindungn.a.
DesignPräklinisch
”Kernaussage
Präklinische Studie zeigt, dass Endocannabinoide Apoptose in Endometriose- und Adenomyose-Gewebe modulieren können; CB1/CB2-Rezeptor-Agonisten zeigen in Zelllinien dosisabhängige pro-apoptotische Effekte.
Zusammenfassung
In-vitro-Studie an humanen endometrialen Stromazellen und Epithelzellen von Endometriose- und Adenomyose-Patientinnen; Endocannabinoide (Anandamid, 2-AG) modulieren Apoptose über CB1/CB2-Rezeptoren, signifikante Reduktion der Zellviabilität bei höheren Konzentrationen (p0.05), mechanistische Hinweise auf antiproliferative Effekte.
P
PopulationPatientinnen mit Endometriose und Adenomyose (Gewebeproben); in vitro: Ishikawa-Zelllinie (Endometriumkarzinom) und CRL-7566 (ovariale Endometriose-Stromazellen)
I
InterventionCB1- und CB2-Rezeptor-Agonisten (in vitro, dosisabhängig)
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.