Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin

Greco, O. and Powell, T.M. and Marples, B. and Joiner, M.C. and Scott, S.D. (2005) Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin. Cancer Gene Therapy, 12 (7). pp. 655-662. ISSN 0929-1903. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1038/sj.cgt.7700834

Abstract

Combining gene therapy with radiotherapy and chemotherapy holds potential to increase the efficacy of cancer treatment, while minimizing side effects. We tested the responsiveness of synthetic gene promoters containing CArG elements from the Early Growth Response 1 (Egr1) gene after neutron irradiation, doxorubicin and cisplatin. Human MCF-7 breast adenocarcinoma and U373-MG glioblastoma cells were transfected with plasmids containing CArG promoters controlling the expression of the green fluorescent protein (GFP). Exposing the cells to neutrons, doxorubicin or cisplatin resulted in a significant induction of transgene expression. Therapeutic advantage was demonstrated by replacing the reporter with the herpes simplex virus thymidine kinase (HSVtk), able to convert the prodrug ganciclovir (GCV) into a cytotoxin. A 1.3 Gy neutron dose caused 49% growth inhibition in MCF-7 cells, which increased to 63% in irradiated CArG-HSVtk-transfectants treated with GCV. Exposure to 0.5 mM cisplatin or 0.01 mM doxorubicin induced a growth inhibition of 25 - 30% in MCF-7 cells. In the presence of GCV, this value increased to 65 - 70% in cells transfected with the CArG promoter constructs driving the expression of HSVtk. These data indicate that combining CArG-mediated HSVtk/ GCV suicide gene therapy with radio- and chemotherapy can enhance antitumor toxicity, and validates future in vivo investigations.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 13 Sep 2008 19:15
Last Modified: 14 Jan 2010 14:36
Resource URI: http://kar.kent.ac.uk/id/eprint/9641 (The current URI for this page, for reference purposes)
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