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Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells
Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603674/ https://www.ncbi.nlm.nih.gov/pubmed/23533367 http://dx.doi.org/10.1155/2013/951343 |
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author | Li, Lei-qing Shen, Fang Xu, Xiao-yan Zhang, Hong Yang, Xiao-feng Liu, Wei-guo |
author_facet | Li, Lei-qing Shen, Fang Xu, Xiao-yan Zhang, Hong Yang, Xiao-feng Liu, Wei-guo |
author_sort | Li, Lei-qing |
collection | PubMed |
description | Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting. |
format | Online Article Text |
id | pubmed-3603674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-36036742013-03-26 Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells Li, Lei-qing Shen, Fang Xu, Xiao-yan Zhang, Hong Yang, Xiao-feng Liu, Wei-guo ScientificWorldJournal Research Article Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting. Hindawi Publishing Corporation 2013-03-03 /pmc/articles/PMC3603674/ /pubmed/23533367 http://dx.doi.org/10.1155/2013/951343 Text en Copyright © 2013 Lei-qing Li et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Lei-qing Shen, Fang Xu, Xiao-yan Zhang, Hong Yang, Xiao-feng Liu, Wei-guo Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title | Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title_full | Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title_fullStr | Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title_full_unstemmed | Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title_short | Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells |
title_sort | gene therapy with hsv1-sr39tk/gcv exhibits a stronger therapeutic efficacy than hsv1-tk/gcv in rat c6 glioma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603674/ https://www.ncbi.nlm.nih.gov/pubmed/23533367 http://dx.doi.org/10.1155/2013/951343 |
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