+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Cell death of human oral squamous cell carcinoma cell line induced by herpes simplex virus thymidine kinase gene and ganciclovir



Cell death of human oral squamous cell carcinoma cell line induced by herpes simplex virus thymidine kinase gene and ganciclovir



Nagoya Journal of Medical Science 66(3-4): 129-137



Suicide gene therapy combining herpes simplex virus thymidine kinase gene (HSVtk) and ganciclovir (GCV) is one strategy for the treatment of head and neck squamous cell carcinoma (HNSCC). The purpose of this study is to determine the mechanism of cell death that occurs in suicide gene therapy using HSVtk and GCV and to assess the safety of that therapy. The human oral squamous cell carcinoma cell line SAS was treated with adenovirus vector containing HSVtk gene (AdHSVtk) and GCV in vitro. Morphological changes including chromatin condensation, cell shrinkage, blebbing of cell membrane, and ballooning formations were observed. Changes in the localization of phospholipids in the cell membrane were also observed. The results of flow cytometry showed a maximum of about 65% of cells in the early phase of apoptosis. In addition, DNA fragmentation was investigated using the TUNEL method in vivo. Nude mice (BALB/c AJD(-nu-), aged 4 weeks) were implanted with SAS and treated with AdHSVtk and GCV. Tumor sections were then observed. The treatment group was confirmed to have DNA fragmentation-positive cells. These results suggest that suicide gene therapy using AdHSVtk and GCV led to apoptosis of the oral squamous cell carcinoma cell line.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 048470017

Download citation: RISBibTeXText

PMID: 14727689


Related references

Tumor reduction in vivo after adenoviral mediated gene transfer of the herpes simplex virus thymidine kinase gene and ganciclovir treatment in human head and neck squamous cell carcinoma. Otolaryngology--Head and Neck Surgery 119(4): 331-336, 1998

Consequences of chemoresistance for the herpes simplex virus thymidine kinase/ganciclovir-induced bystander effect in a human small cell lung cancer cell line model. Anticancer Research 25(1a): 255-261, 2005

Cell death induction of thymidine kinase gene transfer followed by ganciclovir treatment in oral squamous cell carcinoma cell lines. Yonago Acta Medica 48(3): 63-74, 2005

Selective Targeting of a Head and Neck Squamous Cell Carcinoma Cell Line by a Translationally-Controlled Herpes Simplex Virus Thymidine Kinase Suicide Gene. Journal of Oral and Maxillofacial Surgery 65(9-Supp-S): 4100-41000, 2007

Herpes simplex virus thymidine kinase/ganciclovir-induced cell death is enhanced by co-expression of caspase-3 in ovarian carcinoma cells. Cancer Gene Therapy 8(4): 308-319, 2001

Increased bax expression is associated with cell death induced by ganciclovir in a herpes thymidine kinase gene-expressing glioma cell line. Human Gene Therapy 10(4): 679-688, 1999

Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment. Journal of Surgical Oncology 76(1): 19-25, 2001

Transfection of oral cancer cells mediated by transferrin-associated lipoplexes: mechanisms of cell death induced by herpes simplex virus thymidine kinase/ganciclovir therapy. Biochimica et Biophysica Acta 1758(11): 1703-1712, 2006

Virus-free transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment induces tumor cell death. Clinical Cancer Research 2(1): 47-51, 1996

Retrovirus-mediated herpes simplex virus thymidine kinase gene transduction renders human thyroid carcinoma cell lines sensitive to ganciclovir and radiation in vitro and in vivo. Endocrinology 138(11): 4577-4583, 1997

All-trans retinoic acid augments the bystander effect of herpes simplex virus thymidine kinase/ganciclovir system in the treatment of tongue carcinoma cell line. Zhonghua Kou Qiang Yi Xue Za Zhi 38(1): 24-26, 2003

Connexin-independent ganciclovir-mediated killing conferred on bystander effect-resistant cell lines by a herpes simplex virus-thymidine kinase-expressing colon cell line. Molecular Therapy 2(5): 515-523, 2000

Rat adenocarcinoma cell line infected with an adenovirus carrying a novel herpes-simplex virus-thymidine kinase suicide gene construct dies by apoptosis upon treatment with ganciclovir. Journal of Surgical Research 143(1): 189-194, 2007

DNA-liposome complexes transduction of herpes simplex virus thymidine kinase renders human tongue cancer cell line sensitive to ganciclovir in vitro. Chinese Journal of Dental Research 3(4): 44-48, 2000

Cell-specific induction of sensitivity to ganciclovir in medullary thyroid carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase. Endocrinology 141(5): 1814-1822, 2000