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p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts

Ovarian and uterine serous cancers are extremely lethal diseases that often present at an advanced stage. The late-stage diagnosis of these patients results in the metastasis of their cancers throughout the peritoneal cavity leading to death. Improving survival for these patients will require identi...

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Autores principales: Mills, Kathryn A., Quinn, Jeanne M., Roach, S. Tanner, Palisoul, Marguerite, Nguyen, Mai, Noia, Hollie, Guo, Lei, Fazal, Jawad, Mutch, David G., Wickline, Samuel A., Pan, Hua, Fuh, Katherine C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423014/
https://www.ncbi.nlm.nih.gov/pubmed/30886159
http://dx.doi.org/10.1038/s41598-019-41122-3
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author Mills, Kathryn A.
Quinn, Jeanne M.
Roach, S. Tanner
Palisoul, Marguerite
Nguyen, Mai
Noia, Hollie
Guo, Lei
Fazal, Jawad
Mutch, David G.
Wickline, Samuel A.
Pan, Hua
Fuh, Katherine C.
author_facet Mills, Kathryn A.
Quinn, Jeanne M.
Roach, S. Tanner
Palisoul, Marguerite
Nguyen, Mai
Noia, Hollie
Guo, Lei
Fazal, Jawad
Mutch, David G.
Wickline, Samuel A.
Pan, Hua
Fuh, Katherine C.
author_sort Mills, Kathryn A.
collection PubMed
description Ovarian and uterine serous cancers are extremely lethal diseases that often present at an advanced stage. The late-stage diagnosis of these patients results in the metastasis of their cancers throughout the peritoneal cavity leading to death. Improving survival for these patients will require identifying therapeutic targets, strategies to target them, and means to deliver therapies to the tumors. One therapeutic target is the protein AXL, which has been shown to be involved in metastasis in both ovarian and uterine cancer. An effective way to target AXL is to silence its expression with small interfering RNA (siRNA). We investigate the ability of the novel siRNA delivery platform, p5RHH, to deliver anti-AXL siRNA (siAXL) to tumor cells both in vitro and in vivo as well as examine the phenotypic effects of this siRNA interference. First, we present in vitro assays showing p5RHH-siAXL treatment reduces invasion and migration ability of ovarian and uterine cancer cells. Second, we show p5RHH nanoparticles target to tumor cells in vivo. Finally, we demonstrate p5RHH-siAXL treatment reduces metastasis in a uterine cancer mouse xenograft model, without causing an obvious toxicity. Collectively, these findings suggest that this novel therapy shows promise in the treatment of ovarian and uterine cancer patients.
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spelling pubmed-64230142019-03-26 p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts Mills, Kathryn A. Quinn, Jeanne M. Roach, S. Tanner Palisoul, Marguerite Nguyen, Mai Noia, Hollie Guo, Lei Fazal, Jawad Mutch, David G. Wickline, Samuel A. Pan, Hua Fuh, Katherine C. Sci Rep Article Ovarian and uterine serous cancers are extremely lethal diseases that often present at an advanced stage. The late-stage diagnosis of these patients results in the metastasis of their cancers throughout the peritoneal cavity leading to death. Improving survival for these patients will require identifying therapeutic targets, strategies to target them, and means to deliver therapies to the tumors. One therapeutic target is the protein AXL, which has been shown to be involved in metastasis in both ovarian and uterine cancer. An effective way to target AXL is to silence its expression with small interfering RNA (siRNA). We investigate the ability of the novel siRNA delivery platform, p5RHH, to deliver anti-AXL siRNA (siAXL) to tumor cells both in vitro and in vivo as well as examine the phenotypic effects of this siRNA interference. First, we present in vitro assays showing p5RHH-siAXL treatment reduces invasion and migration ability of ovarian and uterine cancer cells. Second, we show p5RHH nanoparticles target to tumor cells in vivo. Finally, we demonstrate p5RHH-siAXL treatment reduces metastasis in a uterine cancer mouse xenograft model, without causing an obvious toxicity. Collectively, these findings suggest that this novel therapy shows promise in the treatment of ovarian and uterine cancer patients. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6423014/ /pubmed/30886159 http://dx.doi.org/10.1038/s41598-019-41122-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mills, Kathryn A.
Quinn, Jeanne M.
Roach, S. Tanner
Palisoul, Marguerite
Nguyen, Mai
Noia, Hollie
Guo, Lei
Fazal, Jawad
Mutch, David G.
Wickline, Samuel A.
Pan, Hua
Fuh, Katherine C.
p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title_full p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title_fullStr p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title_full_unstemmed p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title_short p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
title_sort p5rhh nanoparticle-mediated delivery of axl sirna inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423014/
https://www.ncbi.nlm.nih.gov/pubmed/30886159
http://dx.doi.org/10.1038/s41598-019-41122-3
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