Andrea Tinelli*, Ioannis P. Kosmas, Ospan A. Mynbaev, Antonio Malvasi, Radmila Sparic and Daniele Vergara Pages 310 - 317 ( 8 )
Uterine Fibroids (UFs), or leiomyomas, represent the most frequent pelvic tumor in reproductive-aged women. Although of benign origin, UFs decrease fertility and cause significant reproductive dysfunctions. Compared to normal myometrium, UFs are characterized by a clinical and molecular heterogeneity as demonstrated by the presence of multiple genetic alterations and altered signaling pathways. Recently, selective progesteronereceptor modulators (SPRM), as ulipristal acetate (UPA), have demonstrated their clinical benefits by reducing tumor growth and extracellular matrix deposition. For these reasons, UPA is used in the clinical practice as an intermittent treatment for women symptomatic for UFs or, sometimes, before a myomectomy. However, drug effects on signaling pathways frequently upregulated in UFs remain largely unknown. In fact, the mechanisms of action of the UPA on UFs and on the surrounding areas are not yet understood. To learn more about UPA molecular mechanisms, UF samples were treated ex vivo with UPA and profiled for drug effects on selected markers. During this preliminary ex vivo UPA administration, significant changes were observed in the expression levels of proteins related to cell cycle regulation, cytoskeleton remodeling, and drug resistance. The UPA administration reduced cofilin, Erk and Src phosphorylation, p27 and ezrin protein levels, but not Akt phosphorylation and cyclin D1 and β-catenin levels. This preliminary ex vivo biological analysis provided new insights into the mechanism of action of UPA in the treatment of UFs, which could better explain the biological functioning of the drug on UFs.
Uterine fibroids, leiomyoma, selective progesterone-receptor modulators, ulipristal acetate, progesterone, myometrium.
Department of Obstetrics and Gynecology, Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Vito Fazzi Hospital, P.zza Muratore, Lecce, Ioannina State General Hospital G. Hatzikosta, Department of Obstetrics and Gynecology, University of Ioannina, Laboratory of Human Physiology, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Department of Obstetrics & Gynecology, Santa Maria Hospital, GVM Care & Research, Bari, Clinic of Gynecology and Obstetrics, Clinical Center of Serbia, Višegradska 26, 11000 Belgrade, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce