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Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases
BACKGROUND: Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711931/ https://www.ncbi.nlm.nih.gov/pubmed/23835136 http://dx.doi.org/10.1186/1471-2407-13-338 |
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author | Kedinger, Valerie Meulle, Aline Zounib, Omar Bonnet, Marie-Elise Gossart, Jean-Baptiste Benoit, Elodie Messmer, Melanie Shankaranarayanan, Pattabhiraman Behr, Jean-Paul Erbacher, Patrick Bolcato-Bellemin, Anne-Laure |
author_facet | Kedinger, Valerie Meulle, Aline Zounib, Omar Bonnet, Marie-Elise Gossart, Jean-Baptiste Benoit, Elodie Messmer, Melanie Shankaranarayanan, Pattabhiraman Behr, Jean-Paul Erbacher, Patrick Bolcato-Bellemin, Anne-Laure |
author_sort | Kedinger, Valerie |
collection | PubMed |
description | BACKGROUND: Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics. METHODS: We used our newly developed sticky siRNA-based technology delivered with linear polyethyleneimine (PEI) to inhibit the expression of survivin and cyclin B1 both in vitro and in vivo, and addressed the effect of this inhibition on B16-F10 murine melanoma tumor development. RESULTS: We confirm that survivin and cyclin B1 downregulation through a RNA interference mechanism induces a blockage of the cell cycle as well as impaired proliferation of B16-F10 cells in vitro. Most importantly, PEI-mediated systemic delivery of sticky siRNAs against survivin and cyclin B1 efficiently blocks growth of established subcutaneaous B16-F10 tumors as well as formation and dissemination of melanoma lung metastases. In addition, we highlight that inhibition of survivin expression increases the effect of doxorubicin on lung B16-F10 metastasis growth inhibition. CONCLUSION: PEI-mediated delivery of sticky siRNAs targeting genes involved in tumor progression such as survivin and cyclin B1, either alone or in combination with chemotherapeutic drugs, represents a promising strategy for melanoma treatment. |
format | Online Article Text |
id | pubmed-3711931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37119312013-07-16 Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases Kedinger, Valerie Meulle, Aline Zounib, Omar Bonnet, Marie-Elise Gossart, Jean-Baptiste Benoit, Elodie Messmer, Melanie Shankaranarayanan, Pattabhiraman Behr, Jean-Paul Erbacher, Patrick Bolcato-Bellemin, Anne-Laure BMC Cancer Research Article BACKGROUND: Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics. METHODS: We used our newly developed sticky siRNA-based technology delivered with linear polyethyleneimine (PEI) to inhibit the expression of survivin and cyclin B1 both in vitro and in vivo, and addressed the effect of this inhibition on B16-F10 murine melanoma tumor development. RESULTS: We confirm that survivin and cyclin B1 downregulation through a RNA interference mechanism induces a blockage of the cell cycle as well as impaired proliferation of B16-F10 cells in vitro. Most importantly, PEI-mediated systemic delivery of sticky siRNAs against survivin and cyclin B1 efficiently blocks growth of established subcutaneaous B16-F10 tumors as well as formation and dissemination of melanoma lung metastases. In addition, we highlight that inhibition of survivin expression increases the effect of doxorubicin on lung B16-F10 metastasis growth inhibition. CONCLUSION: PEI-mediated delivery of sticky siRNAs targeting genes involved in tumor progression such as survivin and cyclin B1, either alone or in combination with chemotherapeutic drugs, represents a promising strategy for melanoma treatment. BioMed Central 2013-07-09 /pmc/articles/PMC3711931/ /pubmed/23835136 http://dx.doi.org/10.1186/1471-2407-13-338 Text en Copyright © 2013 Kedinger et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kedinger, Valerie Meulle, Aline Zounib, Omar Bonnet, Marie-Elise Gossart, Jean-Baptiste Benoit, Elodie Messmer, Melanie Shankaranarayanan, Pattabhiraman Behr, Jean-Paul Erbacher, Patrick Bolcato-Bellemin, Anne-Laure Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title | Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title_full | Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title_fullStr | Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title_full_unstemmed | Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title_short | Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
title_sort | sticky sirnas targeting survivin and cyclin b1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711931/ https://www.ncbi.nlm.nih.gov/pubmed/23835136 http://dx.doi.org/10.1186/1471-2407-13-338 |
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