Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway.

放射疗法是一种用于许多癌症的公认治疗方法。然而，抗辐射性仍然是成功治疗的严重障碍。放射治疗后，某些患者的放射抵抗会导致局部复发和远处转移。因此，许多研究试图鉴定有效的放射增敏剂。Eph受体的功能有助于肿瘤发展，调节细胞粘附，侵袭，新血管生成，肿瘤生长和转移。但是，EphA3在放射抗性中的作用仍不清楚。在本研究中，我们建立了稳定的抗辐射头颈癌细胞系（AMC HN3R细胞系），并发现EphA3主要通过DNA芯片，实时PCR和Western印迹法在抗辐射头颈癌细胞系中表达。此外，我们发现EphA3在放射治疗后的复发性喉癌标本中过表达。EphA3介导了抗癌头颈癌细胞株的肿瘤侵袭和迁移以及上皮间充质转化相关蛋白的表达。在体外和体内研究中，抑制EphA3增强了AMC HN 3R细胞系中的放射敏感性。总之，我们的结果表明，EphA3在抗辐射的头颈癌中过表达，并且通过调节上皮间充质转化途径在头颈癌的抗辐射性发展中起关键作用。EphA3介导了抗癌头颈癌细胞株的肿瘤侵袭和迁移以及上皮间充质转化相关蛋白的表达。在体外和体内研究中，抑制EphA3增强了AMC HN 3R细胞系中的放射敏感性。总之，我们的结果表明，EphA3在抗辐射的头颈癌中过表达，并且通过调节上皮间充质转化途径在头颈癌的抗辐射性发展中起关键作用。EphA3介导了抗癌头颈癌细胞株的肿瘤侵袭和迁移以及上皮间充质转化相关蛋白的表达。在体外和体内研究中，抑制EphA3增强了AMC HN 3R细胞系中的放射敏感性。总之，我们的结果表明，EphA3在抗辐射的头颈癌中过表达，并且通过调节上皮间充质转化途径在头颈癌的抗辐射性发展中起关键作用。