{"title":"Dihydroartemisinin enhances the radiosensitivity of breast cancer by targeting ferroptosis signaling pathway through hsa_circ_0001610","authors":"","doi":"10.1016/j.ejphar.2024.176943","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to elucidate how DHA enhances the radiosensitivity of BC and to explain its potential mechanisms of action.</p></div><div><h3>Methods</h3><p>The circular structure of hsa_circ_0001610 was confirmed by Sanger sequencing, RNase R treatment, RT-PCR analysis using gDNA or cDNA. Cellular localization of hsa_circ_0001610 and microRNA-139–5p (miR-139–5p) was detected by fluorescence in situ hybridization. Cell counting kit-8 assay, wound healing and colony formation tests for assessing cell proliferation, while flow cytometry was utilized to estimate cell cycle progression and apoptosis. Reactive oxygen species and malondialdehyde experiments were conducted to validate ferroptosis of BC cells. The expression of ncRNAs and mRNAs was quantified via qRT-PCR, and protein expression was analyzed using Western blot. The effects of hsa_circ_0001610 and DHA on radiosensitivity of BC in vivo were studied by establishing BC mice model.</p></div><div><h3>Results</h3><p>In vivo and in vitro experimental results indicate that DHA promotes ferroptosis of BC cells at least partly by inhibiting hsa_circ_0001610/miR-139–5p/SLC7A11 pathway, thereby enhancing the radiosensitivity of BC cells.</p></div><div><h3>Conclusions</h3><p>Our findings showed that DHA can induce ferroptosis of BC cells by down-regulation of hsa_circ_0001610, thus enhancing radiosensitivity, suggesting a promising therapeutic strategy for enhancing BC radiosensitivity that is worthy of further exploration.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299924006320","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
This study aimed to elucidate how DHA enhances the radiosensitivity of BC and to explain its potential mechanisms of action.
Methods
The circular structure of hsa_circ_0001610 was confirmed by Sanger sequencing, RNase R treatment, RT-PCR analysis using gDNA or cDNA. Cellular localization of hsa_circ_0001610 and microRNA-139–5p (miR-139–5p) was detected by fluorescence in situ hybridization. Cell counting kit-8 assay, wound healing and colony formation tests for assessing cell proliferation, while flow cytometry was utilized to estimate cell cycle progression and apoptosis. Reactive oxygen species and malondialdehyde experiments were conducted to validate ferroptosis of BC cells. The expression of ncRNAs and mRNAs was quantified via qRT-PCR, and protein expression was analyzed using Western blot. The effects of hsa_circ_0001610 and DHA on radiosensitivity of BC in vivo were studied by establishing BC mice model.
Results
In vivo and in vitro experimental results indicate that DHA promotes ferroptosis of BC cells at least partly by inhibiting hsa_circ_0001610/miR-139–5p/SLC7A11 pathway, thereby enhancing the radiosensitivity of BC cells.
Conclusions
Our findings showed that DHA can induce ferroptosis of BC cells by down-regulation of hsa_circ_0001610, thus enhancing radiosensitivity, suggesting a promising therapeutic strategy for enhancing BC radiosensitivity that is worthy of further exploration.
研究目的本研究旨在阐明DHA如何增强BC的放射敏感性,并解释其潜在的作用机制:方法:通过桑格测序、RNase R处理、使用gDNA或cDNA进行RT-PCR分析,确认了hsa_circ_0001610的环状结构。荧光原位杂交法检测了 hsa_circ_0001610 和 microRNA-139-5p (miR-139-5p)的细胞定位。细胞计数试剂盒-8测定、伤口愈合和集落形成测试用于评估细胞增殖,而流式细胞仪则用于评估细胞周期进展和细胞凋亡。活性氧和丙二醛实验验证了 BC 细胞的铁变态反应。通过 qRT-PCR 对 ncRNAs 和 mRNAs 的表达进行了定量,并使用 Western 印迹分析了蛋白质的表达。通过建立 BC 小鼠模型,研究了 hsa_circ_0001610 和 DHA 对 BC 体内放射敏感性的影响:体内和体外实验结果表明,DHA至少部分通过抑制hsa_circ_0001610/miR-139-5p/SLC7A11通路促进BC细胞的铁变态反应,从而提高BC细胞的放射敏感性:我们的研究结果表明,DHA可通过下调hsa_circ_0001610诱导BC细胞的铁变态反应,从而增强其放射敏感性,这为增强BC细胞放射敏感性提供了一种有前景的治疗策略,值得进一步探索。
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.