Department of Otorhinolaryngology and Head and Neck Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
Head Neck. 2014 Mar;36(3):411-8. doi: 10.1002/hed.23309. Epub 2013 Jun 1.
Radioresistance remains a critical issue in the use of radiotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy of combination treatment with OBP-301, a telomerase-specific replication-selective adenovirus, and radiotherapy in overcoming radioresistance by examining its effect on radiation-resistant HNSCC cells.
Radiation-resistant HNSCC cells were treated with OBP-301 and radiation in vitro and in an orthotopic nude mouse model in vivo and synergism was assessed. Apoptosis and expression of MRN complex, which plays a key role in DNA repair machinery, were also analyzed.
Infection with OBP-301 was found to enhance the antitumor efficacy of radiation both in vitro and in vivo by inhibiting MRN complex expression and increasing apoptosis induction.
Combined OBP-301 and radiation therapy seems to overcome radioresistance in HNSCC cells by inhibiting DNA repair machinery, and may thus be a novel therapeutic strategy for treating HNSCC.
放射抵抗仍然是头颈部鳞状细胞癌（HNSCC）放射治疗的一个关键问题。本研究通过研究其对放射抵抗性 HNSCC 细胞的作用，评估了 OBP-301（一种端粒酶特异性复制选择性腺病毒）联合放射治疗克服放射抵抗的疗效。
体外和体内在原位裸鼠模型中用 OBP-301 和放射治疗放射抵抗性 HNSCC 细胞，并评估协同作用。还分析了在 DNA 修复机制中起关键作用的 MRN 复合物的凋亡和表达。
发现 OBP-301 感染通过抑制 MRN 复合物表达和增加凋亡诱导，增强了体外和体内放射治疗的抗肿瘤疗效。
联合 OBP-301 和放射治疗似乎通过抑制 DNA 修复机制克服了 HNSCC 细胞的放射抵抗，因此可能是治疗 HNSCC 的一种新的治疗策略。
