SELENBP1 Inhibits the Malignant Progression and Radioresistance of Nasopharyngeal Carcinoma Cells Through the KEAP1-NRF2 Signaling Pathway.

Abstract

Radiotherapy is the primary treatment modality for patients with nasopharyngeal carcinoma (NPC); however, radioresistance remains a significant challenge, contributing to treatment failure in over 20% of cases. Therefore, elucidating the mechanisms underlying radioresistance is essential. Although selenium-binding protein 1 (SELENBP1) is known to be dysregulated in various human malignancies, its role in NPC radioresistance has not yet been clarified. In this study, Cell Counting Kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and flow cytometry were performed to investigate the association between SELENBP1 expression and NPC progression and radioresistance. Western blotting was conducted to evaluate the activity of the SELENBP1 and KEAP1-NRF2 signaling pathways. Our results demonstrated that SELENBP1 expression was significantly downregulated in NPC cell lines (CEN-2, 5-8F, HK1, and C666-1). Elevated SELENBP1 expression was inversely associated with NPC cell proliferation, migration, and invasion. Furthermore, SELENBP1 overexpression enhanced the radiosensitivity of NPC cells and synergistically promoted apoptosis following radiation exposure. Mechanistically, SELENBP1 exerted its anti-tumor and radiosensitizing effects by regulating the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid2-related factor 2 (NRF2) signaling pathway. In conclusion, SELENBP1 suppresses NPC cell proliferation, migration, invasion and radioresistance via the KEAP1-NRF2 signaling pathway, suggesting that SELENBP1 could be a potential therapeutic target to enhance the radiosensitivity of NPC.