Korean J Gynecol Oncol Colposc.
2003 Sep;14(3):195-201.
Adenovirus-Mediated Thymidine Kinase Gene Transfer with Exposure of Ganciclovir to Uterine Cervical Cancer Cells
- Affiliations
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- 1Department of Obstetrics and Gynecology, Our Lady of Mercy Hospital, Catholic University Medical College, Incheon, Korea.
- 2Department of Obstetrics and Gynecology, Kangnam St. Mary's Hospital, Catholic University Medical College, Seoul, Korea.
Abstract
OBJECTIVE
Although herpes simplex virus thymidine kinase gene (HSVtk) transfer with ganciclovir (GCV) represents the commonly used suicide gene therapy of human cancers, little is known about the feasibility of this approach for the treatment of human uterine cervical cancers. We studied effects of HSVtk plus GCV gene therapy on human uterine cervical cancer in vitro.
METHODS
Three cell lines (HeLa cells, CaSki cells and CUMC-3 cells) from squamous carcinoma of uterine cervix were used. Cells were infected with recombinant adenovirus, containing herpes simplex virus thymidine kinase gene (Ad5RSV-tk) and 10 microgram/ml of GCV was added to media to test whether infection of Ad5RSV-tk would render cervical cancer cells sensitive to cell killing by GCV. For assessment of the bystander effect, infected cells were mixed with uninfected cells at varying ratios (0%, 25%, 50%, 75%, 100%) and GCV was added to media. After 6 days, this was followed by MTT assay.
RESULTS
More than 50% of cell death was observed with an MOI of 3 in HeLa cells and with an MOI of 6 in CaSki cells. CUMC-3 cells showed less sensitivity (MOI of 25) to HSVtk plus GCV therapy in comparison with other two cell lines. 70-80% of cell death was achieved with 25% Ad5RSV-tk infected cells in mixture in all cell line, indicating the presence of a bystander effect.
CONCLUSION
The transfer of HSVtk gene to cervical cancer cells was capable of mediating cell death in vitro, but the bystander effect appeared to be moderate. These findings should be taken into account for the future planning for HSVtk plus GCV gene therapy trials for human uterine cervical cancers.
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