Potential of Varicella zoster virus thymidine kinase as a suicide gene in breast cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1997-06

AUTHORS

C Grignet-Debrus, C M Calberg-Bacq

ABSTRACT

To investigate the potential of the thymidine kinase gene from Varicella zoster virus (VZVtk) to act as a suicide gene, VZVtk was transferred via a dicistronic retroviral construct into MCF7, T-47D and MDA-MB-435 human breast cancer cells. The cytotoxicity of antiviral drugs was then evaluated in vitro on the wild-type and transduced cells. Acyclovir and ganciclovir did not show any selective toxicity for the modified cells. In contrast, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was extremely toxic for the VZVtk expressing cells, with IC50 values of 0.6 microM, 0.1 microM and 0.06 microM for MCF7, T-47D and MDA-MB-435 cells, respectively. The selectivity index of BVDU (ie the IC50 value ratio of the wild-type to the VZVtk cells) was 400 for MCF7, 750 for T-47D and 2000 for MDA-MB-435 cells. To test the system in vivo, VZVtk carrying MDA-MB-435 cells were inoculated subcutaneously into nude mice. An intraperitoneal treatment with BVDU administered at the emergence of the tumors, led to a prolonged arrest of the tumor growth and a reduced tumor mass. This effect was BVDU dose-dependent. No bystander effect of BVDU killing could be demonstrated in vitro on mixed populations of VZVtk positive and negative MDA-MB-435 cells. However, an important bystander effect was observed in identical experiments performed on 9L rat gliosarcoma cells infected with the VZVtk-carrying vector. These results demonstrate the efficiency of VZVtk as a suicide gene when BVDU is used as prodrug. The bystander effect measured in vitro, depends however on the tumoral cell type used. More... »

PAGES

560

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3300435

DOI

http://dx.doi.org/10.1038/sj.gt.3300435

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007848358

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9231072


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