Fukui T, Hayashi Y, Kagami H, Yamamoto N, Fukuhara H, Tohnai I, Ueda M, Mizuno M, Yoshida J
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8550, Nagoya, Japan.
Oral Oncol. 2001 Apr;37(3):211-5. doi: 10.1016/s1368-8375(00)00093-2.
The purpose of this study was to test the possibility of gene transfer as a new therapy for oral cancer. Adeno-associated virus (AAV) has already been used in the fields of cystic fibrosis and Parkinson's disease as a potential vector for gene therapy because of its wide host range, high transduction efficiency, and lack of cytopathogenicity. Four human oral squamous cell carcinoma cell lines were transduced with an AAV vector containing the beta-galactosidase gene (AAVlacZ) in vitro. Gene transduction efficiency was from 20 to 50% at a multiplicity of infection (MOI; for the purposes of this study the number of vector genomes per target cell) of 1x10(3), and nearly 100% of each cell line were transduced at an MOI of 1x10(4). Next, four cell lines were transduced with an AAV vector containing the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in nearly 100% tumor cell killing at an MOI of 1x10(4) and from 70 to 80% tumor cell killing at an MOI of 1x10(3). These results suggest that AAV-mediated gene transfer of HSVtk and administration of GCV has potential as a new therapy for oral squamous cell carcinoma.
本研究的目的是测试基因转移作为口腔癌新疗法的可能性。腺相关病毒（AAV）因其宿主范围广、转导效率高且无细胞致病性，已在囊性纤维化和帕金森病领域作为基因治疗的潜在载体被使用。在体外，用携带β-半乳糖苷酶基因（AAVlacZ）的AAV载体转导四种人口腔鳞状细胞癌细胞系。在感染复数（MOI；在本研究中为每个靶细胞的载体基因组数量）为1×10³时，基因转导效率为20%至50%，在MOI为1×10⁴时，每种细胞系几乎100%被转导。接下来，用携带单纯疱疹病毒胸苷激酶（HSVtk）基因的AAV载体转导四种细胞系，该基因使转导的细胞对更昔洛韦（GCV）敏感。随后给予GCV，在MOI为1×10⁴时导致近100%的肿瘤细胞死亡，在MOI为1×10³时导致70%至80%的肿瘤细胞死亡。这些结果表明，AAV介导的HSVtk基因转移和GCV给药具有作为口腔鳞状细胞癌新疗法的潜力。
