LAUSR

Purpose Nasopharyngeal carcinoma (NPC) is a malignant tumor that commonly occurs in southern China and Southeast Asia. Radiation therapy is the main treatment for patients with NPC, and the radioresistance of NPC is an unresolved clinical problem. This study focuses on the mechanism of NPC radioresistance and explores therapeutic targets and research directions for increasing the radiosensitivity of radioresistant cells. Methods We used a gradient dose model to establish radioresistant strains of 6-10B and CNE-2 human NPC cells. Plate colony formation assays were used to verify the radioresistance of the cells. We evaluated the expression of epidermal growth factor receptor (EGFR), lysosome-associated transmembrane protein 4β (LAPTM4B), Beclin1 and the autophagy-related proteins p62, LC3I, and LC3II by Western blot and observed GFP-LC3 puncta by confocal microscopy. The interaction between proteins was verified by immunofluorescence and coimmunoprecipitation analyses. Flow cytometry was performed to detect differences related to the apoptosis of radioresistant strains. Results The EGFR and LAPTM4B expression levels and autophagic flux were higher in radioresistant cells than in nonradioresistant cells, suggesting that EGFR and LAPTM4B are associated with autophagy levels. We observed that EGFR and LAPTM4B interact and stabilize each other in endosomes by confocal microscopy. LAPTM4B knockdown decreased the survival fraction of radioresistant cells and increased apoptosis after exposure to radiation. Coimmunoprecipitation experiments demonstrated that LAPTM4B interacts with Beclin1, which in turn promotes the initiation of autophagy. Conclusion This study illustrates a relationship among EGFR, LAPTM4B and autophagy in radioresistant NPC cell lines. LAPTM4B interacts with EGFR and Beclin 1, which promotes autophagy. LAPTM4B knockdown decreases radioresistance by inhibiting autophagy. This study proposes a possible mechanism for NPC radioresistance and provides a new research direction and theoretical basis for addressing the radioresistance of NPC.