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Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study

Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attract...

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Autores principales: Lin, Kun-Yuan, Cheng, Siao Muk, Tsai, Shing-Ling, Tsai, Ju-Ya, Lin, Chun-Hui, Cheung, Chun Hei Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862386/
https://www.ncbi.nlm.nih.gov/pubmed/27217778
http://dx.doi.org/10.2147/OTT.S101209
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author Lin, Kun-Yuan
Cheng, Siao Muk
Tsai, Shing-Ling
Tsai, Ju-Ya
Lin, Chun-Hui
Cheung, Chun Hei Antonio
author_facet Lin, Kun-Yuan
Cheng, Siao Muk
Tsai, Shing-Ling
Tsai, Ju-Ya
Lin, Chun-Hui
Cheung, Chun Hei Antonio
author_sort Lin, Kun-Yuan
collection PubMed
description Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a “semi-druggable” target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur) expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose) polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and the estrogen receptor-positive tamoxifen-resistant MCF7-TamC3 cancer cells in vitro. In conclusion, the results of this study suggest that delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA is a promising way to target survivin and to treat survivin-expressing cancers in the future.
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spelling pubmed-48623862016-05-23 Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study Lin, Kun-Yuan Cheng, Siao Muk Tsai, Shing-Ling Tsai, Ju-Ya Lin, Chun-Hui Cheung, Chun Hei Antonio Onco Targets Ther Original Research Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a “semi-druggable” target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur) expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose) polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and the estrogen receptor-positive tamoxifen-resistant MCF7-TamC3 cancer cells in vitro. In conclusion, the results of this study suggest that delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA is a promising way to target survivin and to treat survivin-expressing cancers in the future. Dove Medical Press 2016-05-03 /pmc/articles/PMC4862386/ /pubmed/27217778 http://dx.doi.org/10.2147/OTT.S101209 Text en © 2016 Lin et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Lin, Kun-Yuan
Cheng, Siao Muk
Tsai, Shing-Ling
Tsai, Ju-Ya
Lin, Chun-Hui
Cheung, Chun Hei Antonio
Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title_full Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title_fullStr Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title_full_unstemmed Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title_short Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study
title_sort delivery of a survivin promoter-driven antisense survivin-expressing plasmid dna as a cancer therapeutic: a proof-of-concept study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862386/
https://www.ncbi.nlm.nih.gov/pubmed/27217778
http://dx.doi.org/10.2147/OTT.S101209
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