Chenglei Ma, Xiaoyi Lu, Chen Ni, Yu Gao, Fei Yang, Shiwen Chen, Yi Du, Fang Zhao, Ying Cao, Haiwei Huang
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引用次数: 0
Abstract
Cisplatin (DDP)-based chemotherapy is the standard first-line treatment for cervical cancer (CC). However, many patients with CC develop resistance to DDP, either initially or over time. This resistance significantly limits the effectiveness of treatment. Therefore, identifying new therapeutic targets and combination therapies to overcome DDP resistance is a critical need. In this study, we investigated the expression of SLC25A10 in cervical cancer tissues using bioinformatics analysis and partial tissue analysis. We found that SLC25A10 expression was significantly higher in human cervical cancer tissues compared to normal tissues, based on data from The Cancer Genome Atlas (TCGA) and clinical samples. Moreover, increased SLC25A10 expression was associated with adverse clinicopathological characteristics of cervical cancer patients. To explore the functional role of SLC25A10, we conducted a series of in vitro and in vivo experiments. Our results demonstrated that SLC25A10 promotes cervical cancer cell growth, migration, and resistance to DDP. Mechanistically, we found that inhibiting SLC25A10 expression restricted the transport of glutathione (GSH) and reduced the expression of glutathione peroxidase 4 (GPX4). This led to increased intracellular lipid peroxidation and accumulation of reactive oxygen species (ROS), ultimately promoting iron-mediated cell death (ferroptosis) in cervical cancer cells. In conclusion, our findings suggest that SLC25A10 may serve as a novel therapeutic target to overcome cisplatin resistance and enhance the efficacy of chemotherapy in CC. Future studies should focus on further elucidating the role of SLC25A10 in CC and exploring its potential as a therapeutic target in combination with other treatments.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.