Elimination of HER3‑expressing breast cancer cells using aptamer‑siRNA chimeras

Nachreiner,Inga; Hussain,Ahmad Fawzi; Wullner,Ulrich; Machuy,Nikolaus; Meyer,Thomas F.; Fischer,Rainer; Gattenlöhner,Stefan; Meinhold‑Heerlein,Ivo; Barth,Stefan; Tur,Mehmet Kemal

doi:10.3892/etm.2019.7753

Elimination of HER3‑expressing breast cancer cells using aptamer‑siRNA chimeras

Authors:
- Inga Nachreiner
- Ahmad Fawzi Hussain
- Ulrich Wullner
- Nikolaus Machuy
- Thomas F. Meyer
- Rainer Fischer
- Stefan Gattenlöhner
- Ivo Meinhold‑Heerlein
- Stefan Barth
- Mehmet Kemal Tur
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Affiliations: Department of Research and Development, Grünenthal GmbH, D‑52078 Aachen, Germany, Department of Gynecology and Obstetrics, University Hospital Giessen, Justus‑Liebig‑University Giessen, D‑35392 Giessen, Germany, Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology, D‑52074 Aachen, Germany, Department of Molecular Biology, Max Planck Institute for Infection Biology, D‑10117 Berlin, Germany, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, D‑52074 Aachen, Germany, Department of Experimental Pathology and Immunotherapy, Institute of Pathology, University Hospital Giessen, Justus‑Liebig‑University Giessen, D‑35392 Giessen, Germany, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa
Published online on: July 9, 2019 https://doi.org/10.3892/etm.2019.7753
Pages: 2401-2412
Copyright: © Nachreiner et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is the most common cancer in women worldwide. Despite recent developments in breast cancer detection and treatment, 1.38 million women each year are still affected. Breast cancer heterogeneity at the population and single‑cell level, complexity and developing different metastases are setting several challenges to develop efficient breast cancer therapies. RNA interference (RNAi) represents an opportunity to silence gene expression and inhibit specific pathways in cancer cells. In order to reap the full advantages of RNAi‑based therapy, different pathways that sustain cancer cells growth have been targeted using specific siRNAs. The present study investigated the ability of a set of cytotoxic siRNAs to inhibit growth of breast cancer cells. These siRNAs are targeting eukaryotic elongation factor 2 (EEF2), polo‑like kinase 1 (PLK1), G protein‑coupled receptor kinase 4 (GRK4) and sphingosine kinase interacting protein (SKIP5). To facilitate their targeted delivery, the human epidermal growth factor receptor‑3 (HER3)‑specific aptamer A30 was used. The in vitro results described in this work indicate that combining the highly specific HER3 aptamer with cytotoxic siRNAs targeting (EEF2, PLK1, GRK4 and SKIP5) can inhibit its activity and ultimately suppress proliferation of HER3 positive breast cancer cells.

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