Goebel E A, Davidson B L, Zabner J, Graham S M, Kern J A
Department of Otolaryngology-Head and Neck Surgery, University of Iowa College of Medicine, Iowa City, USA.
Ann Otol Rhinol Laryngol. 1996 Jul;105(7):562-7. doi: 10.1177/000348949610500713.
Advanced head and neck squamous cell carcinomas (HNSCCs) have a poor prognosis despite aggressive multimodal therapy. The goal of our study was to test the feasibility of gene transduction as a novel therapy for head and neck cancer. Three human HNSCC cell lines were transduced in vitro with a replication-deficient recombinant adenovirus containing the lacZ marker gene (Ad2/CMV beta gal). Gene transduction efficiency was dependent on multiplicity of infection, duration of exposure to the virus, and viral concentration. Next, the HEp-2 cell line was transduced with an adenoviral vector (Ad.RSVtk) containing the herpes simplex virus thymidine kinase (HSVtk) gene, which, when expressed, sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in complete tumor cell killing. These results suggest that adenovirus-mediated transfer of HSVtk and administration of GCV has potential as a new therapy for HNSCC.
尽管采用了积极的多模式治疗，晚期头颈部鳞状细胞癌（HNSCCs）的预后仍然很差。我们研究的目的是测试基因转导作为一种治疗头颈癌的新疗法的可行性。在体外，用含有lacZ标记基因（Ad2/CMVβ半乳糖苷酶）的复制缺陷型重组腺病毒转导三个人类HNSCC细胞系。基因转导效率取决于感染复数、病毒暴露时间和病毒浓度。接下来，用含有单纯疱疹病毒胸苷激酶（HSVtk）基因的腺病毒载体（Ad.RSVtk）转导HEp-2细胞系，该基因表达时会使转导的细胞对更昔洛韦（GCV）敏感。随后给予GCV导致肿瘤细胞完全被杀灭。这些结果表明，腺病毒介导的HSVtk转移和GCV给药有潜力成为一种治疗HNSCC的新疗法。
