The cyclin-dependent kinase inhibitor p21(cip1/waf1) enhances the cytotoxicity of ganciclovir in HSV-tk transfected ovarian carcinoma cells.
Suicide gene therapy could be an attractive addition to the treatment of ovarian carcinomas, for which acquired chemoresistance frequently results in treatment failure. Here we show that transfection of the HSV-tk gene, followed by incubation with up to 1 mM ganciclovir fails to induce cell death in SKOV3 chemoresistant human ovarian carcinoma cells. However, co-transfection of HSV-tk with Cip1/Waf1 encoding the p21(cip1/waf1) inhibitor of cdks, allows 100 microM ganciclovir to eradicate the population of tumor cells. Potentiation of a drug by co-transfer of HSV-tk with Cip1/Waf1could thus represent another therapeutic approach for tumours that are resistant to conventional therapy.
Ziller
Christelle
C
Laboratoire de Chimie Génétique, CNRS UMR 7514, Université Louis Pasteur Strasbourg I, Faculté de Pharmacie, 74 route du Rhin, BP 24, 67401 Illkirch, France.
Lincet
Hubert
H
Muller
Christian D
CD
Staedel
Cathy
C
Behr
Jean-Paul
JP
Poulain
Laurent
L
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000998:Antiviral Agents / Q000494:pharmacology*; D016923:Cell Death; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D013937:Thymidine Kinase; D015774:Ganciclovir