Applying the herpes simplex virus thymidine kinase/ganciclovir approach to ovarian cancer: an effective in vitro drug-sensitization system.
Ovarian cancer is a major clinical problem with no rewarding treatment protocol currently available. In other malignancies transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cells using a viral vector followed by administration of ganciclovir (GCV) provides a potentially effective strategy for treatment. In this work human ovarian epithelial cancer cell lines were infected with a recombinant adenoviral vector expressing the HSV-tk (AdRSV-tk) and were rendered sensitive to doses of GCV that were 100-200 times less than for untransfected cells. A strong bystander effect was noted with significant killing at a ratio of infected:uninfected cells of only 1:20 and maximal killing at 1:3. Normal human ovarian surface epithelial cells were also highly sensitive to the AdRSV-tk/GCV system. This study demonstrates the potential efficacy of the HSV-tk/GCV approach in ovarian cancer gene therapy.
Al-Hendy
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A
Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Canada.
Auersperg
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N
D000256:Adenoviridae / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D002460:Cell Line; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000473:pathology; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010053:Ovary / Q000166:cytology / Q000473:pathology; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir