Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Oncology, Jingzhou Hospital, Yangtze University, Jingzhou, China.
Head Neck. 2022 Jul;44(7):1576-1587. doi: 10.1002/hed.27053. Epub 2022 Apr 8.
Radioresistance challenges the clinical outcomes of nasopharyngeal carcinoma (NPC). The 3-phosphoinositide-dependent protein kinase 1 (PDK1) is a crucial kinase of PI3K/AKT signaling pathway which has been implicated in the process of radioresistance. However, the role of PDK1 in NPC remains largely unclear.
The expression of PDK1 was determined by immunohistochemistry and Western blot. The effects of RNA interference and pharmacologic inhibitor of PDK1 in combination with irradiation were investigated.
Overexpression of PDK1 was correlated with poor prognosis in patients with NPC. PDK1 depletion enhanced radiosensitivity of NPC cells both in vitro and in vivo. Additionally, a specific PDK1 inhibitor also had the potential to enhance radiosensitivity in radioresistant NPC cells. Mechanistically, PDK1 depletion inhibited various targets of AKT including mTOR and GSK-3β and reversed the epithelial-mesenchymal transition.
These findings indicated that PDK1 might be a potential target for NPC.
放射抗拒性挑战鼻咽癌（NPC）的临床转归。3-磷酸肌醇依赖性蛋白激酶 1（PDK1）是 PI3K/AKT 信号通路的关键激酶，其参与放射抗拒性过程。然而，PDK1 在 NPC 中的作用仍很大程度上不清楚。
通过免疫组织化学和 Western blot 确定 PDK1 的表达。研究了 RNA 干扰和 PDK1 的药理学抑制剂与照射相结合的作用。
PDK1 的过表达与 NPC 患者的不良预后相关。PDK1 耗竭增强 NPC 细胞在体外和体内的放射敏感性。此外，特定的 PDK1 抑制剂也有可能增强放射抗拒性 NPC 细胞的放射敏感性。在机制上，PDK1 耗竭抑制了 AKT 的各种靶标，包括 mTOR 和 GSK-3β，并逆转了上皮-间充质转化。
这些发现表明 PDK1 可能是 NPC 的一个潜在靶点。
