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01-07-2010 | Preclinical study

Coadministration of nanosystems of short silencing RNAs targeting oestrogen receptor α and anti-oestrogen synergistically induces tumour growth inhibition in human breast cancer xenografts

Authors: Céline Bouclier, Véronique Marsaud, Olivia Bawa, Valérie Nicolas, Laurence Moine, Paule Opolon, Jack-Michel Renoir

Published in: Breast Cancer Research and Treatment | Issue 1/2010

Abstract

The suppression of oestrogen receptor α (ERα) functions by silencing RNAs in association with or not with anti-oestrogens (AEs) both in vitro and in breast cancer cell xenografts was assessed. In vitro, a prolonged decrease in ERα protein expression and an enhanced AE-induced inhibition of ERα-mediated transcription, together with antiproliferative activity, were observed. Incorporation of ERα-siRNAs in pegylated nanocapsules (NC) was achieved; and their intravenous injections in MCF-7 xenografts, in contrast to scramble siRNA containing NCs, lead to decrease in ERα protein content and Ki67 labelling in tumour cells. The pure AE RU58668 (RU) both free and entrapped in stealth nanospheres (NS) at very low concentration (8 μg/kg/week) had no effect on tumour growth evolution. However, coinjection of the two nanocarriers potentiated the decrease in ERα protein, concomitantly with decreasing tumour vasculature and glucose transporter-1. These data support that the targeted delivery of ERα-siRNA in breast tumours potentiates the inhibition of E₂-induced proliferative activity by encapsulated AE through enhanced anti-vascular activity. In the hormone-independent MDA-MB-231 xenograft model, RU-NS at 4 mg/kg/week induce also a strong tumour vascular normalisation. Together, these findings suggest that the anti-oestrogen activity of RU as well as that of targeted ERα-siRNA leads to anti-angiogenic activity. Their delivery in stealth nanocarriers may constitute a new anti-cancer therapeutic strategy in solid tumours.

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Title: Coadministration of nanosystems of short silencing RNAs targeting oestrogen receptor α and anti-oestrogen synergistically induces tumour growth inhibition in human breast cancer xenografts
Authors: Céline Bouclier
Véronique Marsaud
Olivia Bawa
Valérie Nicolas
Laurence Moine
Paule Opolon
Jack-Michel Renoir
Publication date: 01-07-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0558-z

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