17B-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

17B-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

WoS Article

The present study suggests and describes theapplication of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins alfa and beta. The delivery system is composed of a cationic liposome envelope containing 17B-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 ERa was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ERa and B exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MT1A, NF-KB1 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-KB1, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.

The present study suggests and describes theapplication of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins alfa and beta. The delivery system is composed of a cationic liposome envelope containing 17B-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 ERa was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ERa and B exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MT1A, NF-KB1 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-KB1, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.

antisense therapy, delivery, glutathione, liposome, malondialdehyde, metallothionein

antisense therapy, delivery, glutathione, liposome, malondialdehyde, metallothionein

HEGER, Z.; GUMULEC, J.; CERNEI, N.; TMEJOVÁ, K.; KOPEL, P.; BALVAN, J.; MASAŘÍK, M.; ZÍTKA, O.; BEKLOVÁ, M.; ADAM, V.; KIZEK, R.

2016

01.02.2015

1021-335X

ONCOLOGY REPORTS

33

2

Hellenic Republic

921

929

9