Title:Depletion of SLC7A11 Sensitizes Nasopharyngeal Carcinoma Cells to
Ionizing Radiation
Volume: 31
Issue: 4
Author(s): Fan Yang, Hongxun Gong, Shiyan Chen, Jianzhong Li, Ning Huang and Maoxin Wang*
Affiliation:
- Department of Otorhinolaryngology - Head and Neck, Fuzong Clinical College of Fujian Medical University, the
900th Hospital of Joint Logistic Support Force of PLA, Fuzhou 350025, China
Keywords:
Ionizing radiation, ferroptosis, nasopharyngeal carcinoma, SLC7A11, NPC cells, HNE-2 cells.
Abstract:
Background: Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma
(NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel
iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting
cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of
NPC cells to IR remains poorly understood.
Objective: This study aimed to explore the association between IR and ferroptosis in NPC, as well
as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells.
Methods: CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and
western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated
NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells.
JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive
Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined
the levels of Fe2+, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione
(GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate
its impact on the ferroptosis of these cells.
Results: IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4,
COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell
viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione
levels, and elevated Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to
IR.
Conclusion: IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially
serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.
