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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
Autoři | |
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Rok publikování | 2015 |
Druh | Článek v odborném periodiku |
Časopis / Zdroj | Oncology Reports |
Fakulta / Pracoviště MU | |
Citace | |
Doi | http://dx.doi.org/10.3892/or.2014.3627 |
Obor | Onkologie a hematologie |
Klíčová slova | antisense therapy; delivery; glutathione; liposome; malondialdehyde; metallothionein |
Popis | 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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