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.

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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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(15)02048-8/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.