Cargando…

Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids

Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using che...

Descripción completa

Detalles Bibliográficos
Autores principales: Pengnam, Supusson, Plianwong, Samarwadee, Patrojanasophon, Prasopchai, Radchatawedchakoon, Widchaya, Yingyongnarongkul, Boon-ek, Opanasopit, Praneet, Charoensuksai, Purin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070967/
https://www.ncbi.nlm.nih.gov/pubmed/33919902
http://dx.doi.org/10.3390/pharmaceutics13040550
_version_ 1783683591652245504
author Pengnam, Supusson
Plianwong, Samarwadee
Patrojanasophon, Prasopchai
Radchatawedchakoon, Widchaya
Yingyongnarongkul, Boon-ek
Opanasopit, Praneet
Charoensuksai, Purin
author_facet Pengnam, Supusson
Plianwong, Samarwadee
Patrojanasophon, Prasopchai
Radchatawedchakoon, Widchaya
Yingyongnarongkul, Boon-ek
Opanasopit, Praneet
Charoensuksai, Purin
author_sort Pengnam, Supusson
collection PubMed
description Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment.
format Online
Article
Text
id pubmed-8070967
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80709672021-04-26 Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids Pengnam, Supusson Plianwong, Samarwadee Patrojanasophon, Prasopchai Radchatawedchakoon, Widchaya Yingyongnarongkul, Boon-ek Opanasopit, Praneet Charoensuksai, Purin Pharmaceutics Article Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment. MDPI 2021-04-14 /pmc/articles/PMC8070967/ /pubmed/33919902 http://dx.doi.org/10.3390/pharmaceutics13040550 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pengnam, Supusson
Plianwong, Samarwadee
Patrojanasophon, Prasopchai
Radchatawedchakoon, Widchaya
Yingyongnarongkul, Boon-ek
Opanasopit, Praneet
Charoensuksai, Purin
Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title_full Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title_fullStr Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title_full_unstemmed Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title_short Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids
title_sort synergistic effect of doxorubicin and sirna-mediated silencing of mcl-1 using cationic niosomes against 3d mcf-7 spheroids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070967/
https://www.ncbi.nlm.nih.gov/pubmed/33919902
http://dx.doi.org/10.3390/pharmaceutics13040550
work_keys_str_mv AT pengnamsupusson synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT plianwongsamarwadee synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT patrojanasophonprasopchai synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT radchatawedchakoonwidchaya synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT yingyongnarongkulboonek synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT opanasopitpraneet synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids
AT charoensuksaipurin synergisticeffectofdoxorubicinandsirnamediatedsilencingofmcl1usingcationicniosomesagainst3dmcf7spheroids