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Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
BACKGROUND: Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622651/ https://www.ncbi.nlm.nih.gov/pubmed/23589689 http://dx.doi.org/10.2147/IJN.S39072 |
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author | An, Songhie Nam, Kihoon Choi, Sunghyun Bai, Cheng Z Lee, Yan Park, Jong-Sang |
author_facet | An, Songhie Nam, Kihoon Choi, Sunghyun Bai, Cheng Z Lee, Yan Park, Jong-Sang |
author_sort | An, Songhie |
collection | PubMed |
description | BACKGROUND: Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model. METHODS AND RESULTS: The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of .40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4′,6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining. CONCLUSION: The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier’s high transfection efficiency (35%–40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells. |
format | Online Article Text |
id | pubmed-3622651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36226512013-04-15 Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic An, Songhie Nam, Kihoon Choi, Sunghyun Bai, Cheng Z Lee, Yan Park, Jong-Sang Int J Nanomedicine Original Research BACKGROUND: Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model. METHODS AND RESULTS: The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of .40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4′,6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining. CONCLUSION: The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier’s high transfection efficiency (35%–40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells. Dove Medical Press 2013 2013-02-25 /pmc/articles/PMC3622651/ /pubmed/23589689 http://dx.doi.org/10.2147/IJN.S39072 Text en © 2013 An et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research An, Songhie Nam, Kihoon Choi, Sunghyun Bai, Cheng Z Lee, Yan Park, Jong-Sang Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title | Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title_full | Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title_fullStr | Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title_full_unstemmed | Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title_short | Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic |
title_sort | nonviral gene therapy in vivo with pam-rg4/apoptin as a potential brain tumor therapeutic |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622651/ https://www.ncbi.nlm.nih.gov/pubmed/23589689 http://dx.doi.org/10.2147/IJN.S39072 |
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