Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity.
Our study focused on the influence of herpes simplex virus thymidine kinase (HSV-tk) expression and ganciclovir (GCV) treatment on the sensitivity of C6 glioma cells to frequently used chemotherapeutic drugs, i.e. adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), and methotrexate (MTX). Transfection with HSV-tk revealed an increased sensitivity to GCV and CDDP and a decreased sensitivity to ADR and MTX. No significant differences were found in sensitivity to 5-FU. Combined treatment in a HSV-tk negative cell line revealed an additive effect when GCV was combined with ADR, whereas an antagonistic effect was found when GCV was combined with CDDP, 5-FU, or MTX. Comparable results were obtained in an HSV-tk positive cell line, apart from CDDP, which showed an additive effect. In conclusion, both HSV-tk transfection and subsequent GCV treatment can influence the sensitivity of tumor cells to various chemotherapeutic drugs in an antagonistic manner. Therefore, combining HSV-tk/GCV gene therapy with chemotherapy might not always be beneficial.
Van Dillen
I J
IJ
Department of Medical Oncology, Groningen University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Mulder
N H
NH
Meijer
C
C
Dam
W A
WA
Kamstra
E
E
De Vries
L
L
Meersma
G J
GJ
Van der Zee
A G J
AG
De Vries
E F J
EF
Vaalburg
W
W
Hospers
G A P
GA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents; D001932:Brain Neoplasms / Q000473:pathology*; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D015774:Ganciclovir / Q000494:pharmacology*; D015316:Genetic Therapy; D005910:Glioma / Q000473:pathology*; D051381:Rats; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics*; D013937:Thymidine Kinase / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir