The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Cell Death Dis. 2018 Apr 1;9(4):432. doi: 10.1038/s41419-018-0409-0.
Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1, previously named LPLUNC1) is highly expressed in the nasopharynx and significantly downregulated in nasopharyngeal carcinoma (NPC). Low expression is also associated with poor prognosis in patients with NPC. Radiotherapy is a routine treatment for NPC; however, radioresistance is a major cause of treatment failure. Thus, we aimed to investigate the role of BPIFB1 in the radioresponse of NPC. Colony formation and cell survival results showed that BPIFB1 sensitized NPC cells to ionizing radiation. VTN, a previously identified BPIFB1-binding protein, was shown to induce cell proliferation and survival, G2/M phase arrest, DNA repair, activation of the ATM-Chk2 and ATR-Chk1 pathways, and anti-apoptotic effects after exposure to radiation, facilitating NPC cell radioresistance. However, BPIFB1 inhibited this VTN-mediated radioresistance, ultimately improving NPC radiosensitivity. In conclusion, this study is the first to demonstrate the functions of BPIFB1 and VTN in the NPC radioresponse. Our findings indicated that promoting BPIFB1 expression and targeting VTN might represent new therapeutic strategies for NPC.
杀菌/通透性增加蛋白家族 B 成员 1（BPIFB1，以前称为 LPLUNC1）在鼻咽部高度表达，在鼻咽癌（NPC）中显著下调。低表达与 NPC 患者的预后不良相关。放射治疗是 NPC 的常规治疗方法；然而，放射抵抗是治疗失败的主要原因。因此，我们旨在研究 BPIFB1 在 NPC 放射反应中的作用。集落形成和细胞存活结果表明，BPIFB1 使 NPC 细胞对电离辐射敏感。VTN 是先前鉴定的 BPIFB1 结合蛋白，在暴露于辐射后显示出诱导细胞增殖和存活、G2/M 期阻滞、DNA 修复、激活 ATM-Chk2 和 ATR-Chk1 途径以及抗细胞凋亡作用，从而促进 NPC 细胞放射抵抗。然而，BPIFB1 抑制了 VTN 介导的放射抵抗，最终提高了 NPC 的放射敏感性。总之，这项研究首次证明了 BPIFB1 和 VTN 在 NPC 放射反应中的作用。我们的研究结果表明，促进 BPIFB1 表达和靶向 VTN 可能代表 NPC 的新治疗策略。
