SLC25A10 promotes cisplatin resistance by inhibiting ferroptosis in cervical cancer.

IF 7 2区 生物学 Q1 CELL BIOLOGY
Chenglei Ma, Xiaoyi Lu, Chen Ni, Yu Gao, Fei Yang, Shiwen Chen, Yi Du, Fang Zhao, Ying Cao, Haiwei Huang
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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.

SLC25A10通过抑制宫颈癌铁下垂促进顺铂耐药。
以顺铂(DDP)为基础的化疗是宫颈癌(CC)的标准一线治疗。然而,许多CC患者在最初或随着时间的推移对DDP产生耐药性。这种耐药性极大地限制了治疗的有效性。因此,确定新的治疗靶点和联合治疗来克服DDP耐药是迫切需要的。本研究采用生物信息学分析和部分组织分析的方法研究了SLC25A10在宫颈癌组织中的表达。基于癌症基因组图谱(TCGA)和临床样本的数据,我们发现SLC25A10在人宫颈癌组织中的表达明显高于正常组织。SLC25A10表达升高与宫颈癌患者的不良临床病理特征相关。为了探究SLC25A10的功能作用,我们进行了一系列体内外实验。我们的研究结果表明,SLC25A10促进宫颈癌细胞的生长、迁移和对DDP的抗性。在机制上,我们发现抑制SLC25A10的表达限制了谷胱甘肽(GSH)的运输,降低了谷胱甘肽过氧化物酶4 (GPX4)的表达。这导致细胞内脂质过氧化和活性氧(ROS)的积累增加,最终促进宫颈癌细胞中铁介导的细胞死亡(铁下垂)。综上所述,我们的研究结果表明,SLC25A10可能作为一种新的治疗靶点,在CC中克服顺铂耐药,提高化疗疗效,未来的研究应进一步阐明SLC25A10在CC中的作用,并探索其作为治疗靶点与其他治疗药物联合的潜力。
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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
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.
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