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

Garcia-Pascual, C M, Ferrero, H, Juarez, I, Martinez, J, Villanueva, A, Pozuelo-Rubio, M, Soengas, M, Tormo, D, Simon, C, Gomez, R, Pellicer, A,
Fertil Steril. Feb. 2016 doi: 10.1016/j.fertnstert.2015.10.037


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.