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

Polyinosinic-polycytidylic acid complexed with polyethylenimine clearly decreased angiogenesis and promoted apoptosis in a mouse model of leiomyoma, but prolonged treatments may be necessary to affect lesion size.

Carmen Maria García-Pascual, Ph.D., Hortensia Ferrero, Ph.D., Irene Juarez, M.D., Jessica Martínez, Ph.D., Ana Villanueva, Ph.D., Mercedes Pozuelo-Rubio, Ph.D., Marisol Soengas, Ph.D., Damiá Tormo, Ph.D., Carlos Simón, MD., Raúl Gómez, Ph.D., Antonio Pellicer, M.D.

Volume 105, Issue 2, Pages 529-538


To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pICPEI] in xenografted human leiomyomas.

Heterologous leiomyoma mouse model.

University-affiliated infertility center.

Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation.

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 [pICPEI] (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.

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 [pICPEI]-treated group versus control.

We hypothesize that the antiangiogenic and apoptotic effects exerted by [pICPEI] 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 [pICPEI] as a potential novel therapeutic agent against human leiomyoma.

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