MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal ca...

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Autores principales:	Passadouro M, Pedroso de Lima MC, Faneca H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c196b8417c2648cfa351d6e706883f28
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spelling	oai:doaj.org-article:c196b8417c2648cfa351d6e706883f282021-12-02T00:40:20ZMicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer1178-2013https://doaj.org/article/c196b8417c2648cfa351d6e706883f282014-07-01T00:00:00Zhttp://www.dovepress.com/microrna-modulation-combined-with-sunitinib-as-a-novel-therapeutic-str-a17449https://doaj.org/toc/1178-2013 Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/–) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexesPassadouro MPedroso de Lima MCFaneca HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3203-3217 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Passadouro M Pedroso de Lima MC Faneca H MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
description	Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/–) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexes
format	article
author	Passadouro M Pedroso de Lima MC Faneca H
author_facet	Passadouro M Pedroso de Lima MC Faneca H
author_sort	Passadouro M
title	MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
title_short	MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
title_full	MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
title_fullStr	MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
title_full_unstemmed	MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
title_sort	microrna modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/c196b8417c2648cfa351d6e706883f28
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MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

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