17β-estradiol-containing liposomes as a novel delivery system for the antisense therapy of ER-positive breast cancer: An in vitro study on the MCF-7 cell line

Heger,Zbynek; Gumulec,Jaromir; Cernei,Natalia; Tmejova,Katerina; Kopel,Pavel; Balvan,Jan; Masarik,Michal; Zitka,Ondrej; Beklova,Miroslava; Adam,Vojtech; Kizek,Rene

doi:10.3892/or.2014.3627

17β-estradiol-containing liposomes as a novel delivery system for the antisense therapy of ER-positive breast cancer: An in vitro study on the MCF-7 cell line

Authors:
- Zbynek Heger
- Jaromir Gumulec
- Natalia Cernei
- Katerina Tmejova
- Pavel Kopel
- Jan Balvan
- Michal Masarik
- Ondrej Zitka
- Miroslava Beklova
- Vojtech Adam
- Rene Kizek
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Affiliations: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic, Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic, Department of Ecology and Diseases of Game, Fish and Bees, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, CZ-612 42 Brno, Czech Republic
Published online on: November 26, 2014 https://doi.org/10.3892/or.2014.3627
Pages: 921-929

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Abstract

The present study suggests and describes the application of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins α and β. The delivery system is composed of a cationic liposome envelope containing 17β-estradiol (E2) in its structure. Cationic liposomes protect cargo against the extracellular matrix, and E2 can increase its shuttling efficiency into cells. Using MCF-7 cells derived from estrogen receptor-positive ductal carcinoma, treatment with liposomes against ERα was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ERα and β exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MT1A, NF-κB1 and K-ras genes, but not TFF1, were downregulated using E2-based liposomes (evaluated at P=0.05). Further indicators of oxidative stress were employed to assess the effect on treatment efficiency. Glutathione (GSH/GSSG redox ratio), metallothionein (MT) and malondialdehyde (MDA) confirmed a positive effect of antisense therapy resulting in their decreased levels in the MCF-7 cells. Based on these data, we suggest that E2-based liposomes offer sufficient transfer efficiency and moreover, due to the effect on NF-κB1, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.

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