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

Capsule:
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.

Authors:
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

Abstract:

Objective:
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.

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 [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.

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 [pICPEI]-treated group versus control.

Conclusion(s):
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.

Translate »