Fertility and sterility · 2015
Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.
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García-Pascual Carmen Maria, Ferrero Hortensia, Juarez Irene, Martínez Jessica, Villanueva Ana, Pozuelo-Rubio Mercedes, Soengas Marisol, Tormo Damiá, Simón Carlos, Gómez Raúl, Pellicer Antonio
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAngiogenesis InhibitorsAnimalsApoptosisCell ProliferationDisease Models, AnimalEstrogen Replacement TherapyFemaleHumansKi-67 AntigenLeiomyomaMice, NudeMiddle AgedNeovascularization, PathologicOvariectomyPlatelet Endothelial Cell Adhesion Molecule-1Poly I-CPolyethyleneimineTime FactorsTumor BurdenTumor Cells, CulturedUterine NeoplasmsXenograft Model Antitumor Assays