SLC2A3 knockdown enhances radiosensitivity and suppresses MAPK signaling in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of epithelial malignancy, where radioresistance significantly hinders effective treatment and favorable prognosis. This study aims to elucidate how solute carrier family 2 member 3 (SLC2A3) influences radiosensitivity and to uncover the underlying mechanisms in NPC. METHODS: HNE1 and NPC/HK-1 cells were exposed to graded doses of irradiation. The effects of SLC2A3 silencing on NPC radiosensitivity were assessed through in vitro functional assays. A xenograft tumor model was established to evaluate the effect of SLC2A3 knockdown on tumor response to fractionated irradiation in vivo. Kaempferol was used as a pharmacological modulator of MAPK signaling to explore the involvement of this pathway in SLC2A3-mediated radiosensitivity. RESULTS: SLC2A3 was significantly overexpressed in NPC cell lines. Silencing SLC2A3 impaired the proliferation, migration, and invasion of NPC cells and increased apoptosis following irradiation. Additionally, SLC2A3 downregulation reduced tumor growth in irradiated NPC xenograft-bearing mice. Under glucose-limited conditions, SLC2A3 silencing impaired glycolytic flux, reduced NPC cell viability, and increased apoptosis. Mechanistically, SLC2A3 knockdown enhanced the radiosensitivity of HNE1 cells, at least partly in association with reduced MAPK pathway activation. CONCLUSION: This study demonstrates that silencing SLC2A3 can improve the sensitivity of NPC to radiation therapy, suggesting a potential therapeutic target for overcoming radioresistance in NPC.