Therapeutic effects of WT1 silencing via respiratory administration of neutral DOPC Liposomal-siRNA in a lung metastasis melanoma murine model

Ramos-Gonzalez, Martin R.; Vazquez-Garza, Eduardo; Garcia-Rivas, Gerardo; Rodriguez-Aguayo, Cristian; Chavez-Reyes, Arturo

Therapeutic effects of WT1 silencing via respiratory administration of neutral DOPC Liposomal-siRNA in a lung metastasis melanoma murine model

dc.contributor.author	Ramos-Gonzalez, Martin R.	es
dc.contributor.author	Vazquez-Garza, Eduardo	es
dc.contributor.author	Garcia-Rivas, Gerardo	es
dc.contributor.author	Rodriguez-Aguayo, Cristian	es
dc.contributor.author	Chavez-Reyes, Arturo	es
dc.date.accessioned	2023-05-18T14:39:23Z
dc.date.available	2023-05-18T14:39:23Z
dc.date.issued	2023-03-22
dc.description.abstract	The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs’ WT1-treated cells when compared with controls, resulting in a loss of the cell’s viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.	en_US
dc.identifier.citation	Non-Coding RNA, Vol. 9, N° 2 (2023)	en_US
dc.identifier.doi	https://doi.org/10.3390/ncrna9020021
dc.identifier.issn	2311-553X
dc.identifier.orcid	https://orcid.org/0000-0002-6655-815X	es
dc.identifier.uri	http://hdl.handle.net/20.500.12254/3253
dc.language.iso	en	en_US
dc.publisher	MDPI	en_US
dc.rights	Atribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject.other	SIRNA	es
dc.subject.other	Melanoma	es
dc.subject.other	Liposomas	es
dc.subject.other	Neoplasia Pulmonar	es
dc.title	Therapeutic effects of WT1 silencing via respiratory administration of neutral DOPC Liposomal-siRNA in a lung metastasis melanoma murine model	en
dc.type	Artículo	es