Department of Traditional Chinese Medicine, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
PLoS One. 2020 Mar 2;15(3):e0229272. doi: 10.1371/journal.pone.0229272. eCollection 2020.
Radiotherapy is one of the major remedies for the treatment of cancer, including nasopharyngeal carcinoma (NPC). Radioresistance occurs very often in target cells that is a large drawback in cancer treated with radiotherapy. Livin involves the over-growth of cancer cells. This study aims to investigate the role of livin in the radioresistance formation in NPC cells.
NPC cell lines were exposed to small doses of irradiation to establish a cell model of radioresistance, in which the role of livin in the development of radioresistance was evaluated.
The expression of livin was observed in NPC cells, which was significantly increased after exposing to small doses of irradiation. A negative correlation was detected between livin and Fas expression in NPC cells. Livin formed a complex with heat shock factor-1 (HSF1, the transcription factor of Fas) in NPC cells after irradiation, which sped up ubiquitination of HSF1. Livin was involved in suppressing Fas expression in NPC cells with radioresistance. Exposure to livin inhibitors prevented radioresistance development and overcame the established radioresistance in NPC cells.
Livin expression in NPC cells plays a critical role in the development of radioresistance. Depletion of livin increases the sensitiveness of NPC cells to irradiation. Target therapy against livin may have the translational potential for the treatment of NPC.
放射治疗是治疗癌症的主要方法之一，包括鼻咽癌（NPC）。放射抵抗经常发生在靶细胞中，这是放射治疗癌症的一个大问题。Livin 涉及癌细胞的过度生长。本研究旨在探讨 Livin 在 NPC 细胞放射抵抗形成中的作用。
用小剂量照射 NPC 细胞系，建立放射抵抗细胞模型，评估 Livin 在放射抵抗发展中的作用。
在 NPC 细胞中观察到 Livin 的表达，在小剂量照射后其表达明显增加。在 NPC 细胞中，Livin 与 Fas 表达呈负相关。照射后 Livin 与热休克因子-1（Fas 的转录因子）在 NPC 细胞中形成复合物，加速 HSF1 的泛素化。Livin 参与抑制 NPC 细胞中的 Fas 表达，导致 NPC 细胞产生放射抵抗。暴露于 Livin 抑制剂可防止 NPC 细胞产生放射抵抗并克服 NPC 细胞中已建立的放射抵抗。
NPC 细胞中 Livin 的表达在放射抵抗的发展中起着关键作用。Livin 的耗竭增加 NPC 细胞对照射的敏感性。针对 Livin 的靶向治疗可能具有治疗 NPC 的转化潜力。
