2026-06-14T03:44:56Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/196152024-11-29T13:25:46Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2022-06-24 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. Cancers (Basel) . 2022 ;14(13):3102. 10.3390/cancers14133102 2072-6694 Cancers 35804874 http://hdl.handle.net/20.500.12105/19615 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.