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RESEARCH PRODUCT

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

Carmen M. García-pascualJessica MartínezMercedes Pozuelo-rubioMarisol SoengasHortensia FerreroIrene JuarezAntonio PellicerAntonio PellicerCarlos SimónRaúl GómezDamiá TormoAna Villanueva

subject

AdultTime FactorsAngiogenesisOvariectomyHeterologousMice NudeAngiogenesis InhibitorsApoptosis03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePeritoneummedicineTumor Cells CulturedAnimalsHumansPolyethyleneimineCell ProliferationPolyethylenimine030219 obstetrics & reproductive medicineLeiomyomaNeovascularization PathologicCell growthbusiness.industryEstrogen Replacement TherapyObstetrics and GynecologyMiddle Agedmedicine.diseaseXenograft Model Antitumor AssaysTumor BurdenTransplantationPlatelet Endothelial Cell Adhesion Molecule-1Disease Models AnimalLeiomyomamedicine.anatomical_structureKi-67 AntigenPoly I-CReproductive MedicinechemistryApoptosis030220 oncology & carcinogenesisImmunologyUterine NeoplasmsCancer researchFemalebusiness

description

Objective To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC PEI ] in xenografted human leiomyomas. Design Heterologous leiomyoma mouse model. Setting University-affiliated infertility center. Animal(s) Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Intervention(s) Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC PEI ] (n = 8) for 4 weeks. Main Outcome Measure(s) The size of the leiomyoma implants, and cellular proliferation (Ki67), vascularization (PECAM), and apoptosis (OH-ends) assessed by quantitative immunohistochemical/immunofluorescent analysis of the recovered implants. Result(s) No significant differences were observed in the size of the leiomyoma implants between groups. Vascularization and proliferation were significantly decreased, and apoptosis was increased in the [pIC PEI ]-treated group versus control. Conclusion(s) We hypothesize that the antiangiogenic and apoptotic effects exerted by [pIC PEI ] might lead to a decrease in lesion size in this animal model if the compound is administered for longer periods of time. This study provides promising data on [pIC PEI ] as a potential novel therapeutic agent against human leiomyoma.

10.1016/j.fertnstert.2015.10.037https://pubmed.ncbi.nlm.nih.gov/26616441