Suicide gene therapy using adenovirus vector for human oral squamous carcinoma cell line in vitro.
Recently, suicide gene therapy using the herpes simplex virus thymidine kinase (HSVtk) gene followed by ganciclovir (GCV) administration was evaluated for the treatment of cancer. The purpose of this study was to investigate the effectiveness of suicide gene therapy using the replication-deficient recombinant adenovirus vector for human oral squamous carcinoma cell lines. To evaluate transduction efficiency, each cell line was transduced in vitro with an adenovirus vector containing the beta-galactosidase gene. By 24 hours after transduction, nearly 100% of the cells were transduced at a multiplicity of infection (MOI) of 10, and from 30 to 10% at an MOI of 1. Next, each cell line was transduced with an adenovirus vector containing the HSVtk gene, and a subsequent administration of GCV for the assessment of suicide gene therapy. A subsequent administration of GCV resulted in complete tumor cell death. In addition, we conducted a morphological analysis of that cell death using video-enhanced contrast differential interference contrast microscopy, and we observed that it included both apoptosis and necrosis after HSVtk gene and GCV treatment. These results suggest that adenovirus-mediated suicide gene therapy induced remarkable cytotoxicity with a bystander effect in human oral squamous cell carcinoma thus suggesting an effective treatment strategy for that tumor.
Yamamoto
Noriyuki
N
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. noriyuki@med.nagoya-u.ac.jp
Hayashi
Yasushi
Y
Kagami
Hideaki
H
Fukui
Takafumi
T
Fukuhara
Hirokazu
H
Tohnai
Iwai
I
Ueda
Minoru
M
Mizuno
Masaaki
M
Yoshida
Jun
J
D000256:Adenoviridae / Q000235:genetics*; D000998:Antiviral Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008048:Lip Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir