文章：

GluOC通过诱导SLC7A11和SLC38A1激活氧化还原过程并抵抗三阴性乳腺癌中的铁死亡

GluOC Induced SLC7A11 and SLC38A1 to Activate Redox Processes and Resist Ferroptosis in TNBC

原文发布日期：21 February 2025

DOI: 10.3390/cancers17050739

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Ferroptosis, a type of programmed cell death, is mainly associated with disruptions in iron metabolism, imbalances in the amino acid antioxidant system, and the build-up of lipid peroxides. Triple-negative breast cancer (TNBC) has a dismal prognosis. Since activating ferroptosis can suppress breast cancer cell proliferation, it holds promise as a novel therapeutic target for breast cancer patients. Thus, the objective of this study was to clarify the mechanism of ferroptosis in TNBC, aiming to find new treatment strategies for TNBC patients. Methods: We screened out the differential genes related to ferroptosis in TNBC after GluOC treatment based on the whole-genome sequencing results. At the cellular level, we conducted explorations using techniques such as quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, fluorescence staining, and siRNA transfection. Moreover, we further verified the role of GluOC in inhibiting ferroptosis in TNBC through in vivo experiments using nude mice. Results: The results showed that GluOC enhanced glutathione expression levels by inducing SLC7A11 accumulation via the specific signaling pathway. Additionally, GluOC increased ATP production and tricarboxylic acid flux resistance to ferroptosis through SLC38A1. Overall, GluOC coordinately regulated SLC7A11 and SLC38A1 to inhibit ferroptosis in TNBC. Conclusions: This study elucidated the mechanism of GluOC in inhibiting ferroptosis in TNBC. The findings not only provided new insights into ferroptosis but also potentially offered new concepts for the development of future anticancer therapies, which may contribute to improving the treatment of TNBC patients.

摘要翻译： 

背景/目的：铁死亡作为一种程序性细胞死亡方式，主要与铁代谢紊乱、氨基酸抗氧化系统失衡及脂质过氧化物积累相关。三阴性乳腺癌预后不良，而激活铁死亡可抑制乳腺癌细胞增殖，有望成为乳腺癌患者的新型治疗靶点。因此，本研究旨在阐明铁死亡在三阴性乳腺癌中的作用机制，以期为三阴性乳腺癌患者探索新的治疗策略。方法：基于全基因组测序结果，我们筛选出GluOC处理后三阴性乳腺癌中与铁死亡相关的差异基因。在细胞层面，通过实时定量聚合酶链反应、蛋白质印迹法、荧光染色及siRNA转染等技术进行机制探索。同时，通过裸鼠体内实验进一步验证GluOC在三阴性乳腺癌中抑制铁死亡的作用。结果：研究显示，GluOC通过特定信号通路诱导SLC7A11积累，从而提升谷胱甘肽表达水平。此外，GluOC通过SLC38A1增加三羧酸循环通量及ATP生成以抵抗铁死亡。总体而言，GluOC通过协同调控SLC7A11与SLC38A1抑制三阴性乳腺癌的铁死亡进程。结论：本研究阐明了GluOC抑制三阴性乳腺癌铁死亡的作用机制，不仅为铁死亡研究提供了新视角，也可能为未来抗癌疗法的开发提供新思路，有望改善三阴性乳腺癌患者的治疗现状。

原文链接：

GluOC Induced SLC7A11 and SLC38A1 to Activate Redox Processes and Resist Ferroptosis in TNBC