17 beta-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

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Authors

HEGER Zbynek GUMULEC Jaromír CERNEI Natalia TMEJOVA Katerina KOPEL Pavel BALVAN Jan MASAŘÍK Michal ZITKA Ondrej BEKLOVA Miroslava ADAM Vojtech KIZEK Rene

Year of publication 2015
Type Article in Periodical
Magazine / Source Oncology Reports
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.3892/or.2014.3627
Field Oncology and hematology
Keywords antisense therapy; delivery; glutathione; liposome; malondialdehyde; metallothionein
Description The present study suggests and describes the application of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins alpha and beta. The delivery system is composed of a cationic liposome envelope containing 17 beta-estradiol (E-2) in its structure. Cationic liposomes protect cargo against the extracellular matrix, and E-2 can increase its shuttling efficiency into cells. Using MCF-7 cells derived from estrogen receptor-positive ductal carcinoma, treatment with liposomes against ER alpha was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ER alpha and beta exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MTIA,NF-kappa B1 and K-ras genes, but not TFF1, were downregulated using E-2-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-kappa BI, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.
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