2026-06-14T03:40:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/196152024-11-29T13:25:46Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Diego-González, Lara
author
Fernández-Carrera, Andrea
author
Igea, Ana
author
Martínez-Pérez, Amparo
author
Real Oliveira, M Elisabete C D
author
Gomes, Andreia C
author
Guerra, Carmen
author
Barbacid, Mariano
author
González-Fernández, África
author
Simón-Vázquez, Rosana
funder
Xunta de Galicia (España)
funder
CRIS contra el Cáncer
funder
Fundación AXA
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
European Union (EU)
2024-05-28T09:38:01Z
2024-05-28T09:38:01Z
2022-06-24
Cancers (Basel) . 2022 ;14(13):3102.
10.3390/cancers14133102
2072-6694
Cancers
35804874
http://hdl.handle.net/20.500.12105/19615
Pancreatic cancer evades most of the current therapies and there is an urgent need for new treatments that could efficiently eliminate this aggressive tumor, such as the blocking of routes driving cell proliferation. In this work, we propose the use of small interfering RNA (siRNA) to inhibit the combined expression of FOSL-1 and YAP, two signaling proteins related with tumor cell proliferation and survival. To improve the efficacy of cell transfection, DODAB:MO (1:2) liposomes were used as siRNA nanocarriers, forming a complex denominated siRNA-lipoplexes. Liposomes and lipoplexes (carrying two siRNA for each targeted protein, or the combination of four siRNAs) were physico-chemically and biologically characterized. They showed very good biocompatibility and stability. The efficient targeting of FOSL-1 and YAP expression at both mRNA and protein levels was first proved in vitro using mouse pancreatic tumoral cell lines (KRASG12V and p53 knockout), followed by in vivo studies using subcutaneous allografts on mice. The peri-tumoral injection of lipoplexes lead to a significant decrease in the tumor growth in both Athymic Nude-Foxn1nu and C57BL/6 mice, mainly in those receiving the combination of four siRNAs, targeting both YAP and FOSL-1. These results open a new perspective to overcome the fast tumor progression in pancreatic cancer.
eng
pancreatic ductal adenocarcinoma
NANOMEDICINE
LIPOSOMES
GENE SILENCING
KRAS
HIPPO PATHWAY
Combined Inhibition of FOSL-1 and YAP Using siRNA-Lipoplexes Reduces the Growth of Pancreatic Tumor.
other
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URL
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combinedinhibitionofFOSL-1.pdf
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text/plain
combinedinhibitionofFOSL-1.pdf.txt