Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Oncol Res. 2013;20(9):419-25. doi: 10.3727/096504013X13657689383139.
Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), and treatment of radioresistant OSCC is difficult due to cross resistance to other conventional treatments. We aimed to identify whether genetically modified oncolytic adenovirus expressing relaxin (RLX), which affects collagen metabolism, can effectively inhibit growth of the radioresistant OSCC. Therapeutic effect of oncolytic adenovirus was compared between radiosensitive and radioresistant OSCC cell lines in vitro and in vivo, and spread of adenovirus throughout the tumor mass was verified by immunohistochemistry (IHC). Oncolytic adenovirus effectively killed cancer cells and there was no significant difference in the cytotoxic effect between radiosensitive and radioresistant OSCC cell lines. In animal experiments, the adenovirus significantly reduced the size of tumor, and there was no significant difference between radiosensitive and radioresistant OSCC. In IHC, RLX expressing adenovirus showed better proliferation and eliminated collagens more effectively compared to RLX nonexpressing adenovirus. These findings suggested that genetically modified oncolytic adenovirus can effectively inhibit growth of the radioresistant OSCC and might be a new therapeutic option in radioresistant OSCC.
放射抗拒性是口腔鳞状细胞癌(OSCC)治疗结果的主要决定因素之一,由于对其他常规治疗的交叉耐药性,治疗放射抗拒性 OSCC 较为困难。我们旨在确定表达松弛素(RLX)的遗传修饰溶瘤腺病毒是否可以有效抑制放射抗拒性 OSCC 的生长,RLX 影响胶原代谢。在体外和体内比较了溶瘤腺病毒对放射敏感和放射抗拒性 OSCC 细胞系的治疗效果,并通过免疫组织化学(IHC)验证了腺病毒在肿瘤中的扩散。溶瘤腺病毒可有效杀死癌细胞,放射敏感和放射抗拒性 OSCC 细胞系之间的细胞毒性作用无明显差异。在动物实验中,腺病毒显著缩小了肿瘤的大小,放射敏感和放射抗拒性 OSCC 之间无明显差异。在 IHC 中,与不表达 RLX 的腺病毒相比,表达 RLX 的腺病毒显示出更好的增殖能力,并能更有效地消除胶原蛋白。这些发现表明,遗传修饰的溶瘤腺病毒可以有效抑制放射抗拒性 OSCC 的生长,可能是放射抗拒性 OSCC 的一种新的治疗选择。