Inhibition of PDK1 enhances radiosensitivity and reverses epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Abstract

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.