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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...

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Autores principales: Li, Lei-qing, Shen, Fang, Xu, Xiao-yan, Zhang, Hong, Yang, Xiao-feng, Liu, Wei-guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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.
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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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