Adenovirus-mediated thymidine kinase gene transduction in human epithelial ovarian cancer cell lines followed by exposure to ganciclovir.
In an effort to develop gene therapy for ovarian cancer efficacy and toxicity of adenovirus-mediated transfer of the HSV-TK gene followed by administration of ganciclovir were studied in two human epithelial ovarian cancer cell lines Ov-ca-2774 and Ov-ca-1225. 100% transduction was achieved in both cell lines at MOIs of 7 and 15 as demonstrated by X-Gal staining. No toxicity of virus alone was observed at MOIs up to 30. GCV was not toxic up to 200 micrograms/ml. Cell killing efficacy was shown to be dependent on MOI as well as GCV dose. The "bystander effect" of ADV/RSV-TK was quantified by mixing experiments and found to be dependent on the proportion of ADV/RSV-TK positive cells as well as the GCV dosage. Similar results were observed in both cell lines. ADV/RSV-TK mediated gene therapy may be a promising approach in ovarian cancer.
Tong
X W
XW
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Block
A
A
Chen
S H
SH
Woo
S L
SL
Kieback
D G
DG
D000256:Adenoviridae; D000963:Antimetabolites / Q000633:toxicity*; D000998:Antiviral Agents / Q000633:toxicity*; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015774:Ganciclovir / Q000633:toxicity*; D006801:Humans; D010051:Ovarian Neoplasms; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D000998:Antiviral Agents; D011994:Recombinant Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir