• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

缺氧诱导因子-1α在光子和碳离子照射后DNA双链断裂的检测、信号传导及修复中的作用

Involvement of HIF-1α in the Detection, Signaling, and Repair of DNA Double-Strand Breaks after Photon and Carbon-Ion Irradiation.

作者信息

Wozny Anne-Sophie, Gauthier Arnaud, Alphonse Gersende, Malésys Céline, Varoclier Virginie, Beuve Michael, Brichart-Vernos Delphine, Magné Nicolas, Vial Nicolas, Ardail Dominique, Nakajima Tetsuo, Rodriguez-Lafrasse Claire

机构信息

Cellular and Molecular Radiobiology Laboratory, Lyon-Sud Medical School, UMR CNRS5822/IP2I, Univ Lyon, Lyon 1 University, 69921 Oullins, France.

Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310 Pierre-Bénite, France.

出版信息

Cancers (Basel). 2021 Jul 30;13(15):3833. doi: 10.3390/cancers13153833.

DOI:10.3390/cancers13153833
PMID:34359734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8345054/
Abstract

Hypoxia-Inducible Factor 1α (HIF-1α), which promotes cancer cell survival, is the main regulator of oxygen homeostasis. Hypoxia combined with photon and carbon ion irradiation (C-ions) stabilizes HIF-1α. Silencing HIF-1α under hypoxia leads to substantial radiosensitization of Head-and-Neck Squamous Cell Carcinoma (HNSCC) cells after both photons and C-ions. Thus, this study aimed to clarify a potential involvement of HIF-1α in the detection, signaling, and repair of DNA Double-Strand-Breaks (DSBs) in response to both irradiations, in two HNSCC cell lines and their subpopulations of Cancer-Stem Cells (CSCs). After confirming the nucleoshuttling of HIF-1α in response to both exposure under hypoxia, we showed that silencing HIF-1α in non-CSCs and CSCs decreased the initiation of the DSB detection (P-ATM), and increased the residual phosphorylated H2AX (γH2AX) foci. While HIF-1α silencing did not modulate 53BP1 expression, P-DNA-PKcs (NHEJ-c) and RAD51 (HR) signals decreased. Altogether, our experiments demonstrate the involvement of HIF-1α in the detection and signaling of DSBs, but also in the main repair pathways (NHEJ-c and HR), without favoring one of them. Combining HIF-1α silencing with both types of radiation could therefore present a potential therapeutic benefit of targeting CSCs mostly present in tumor hypoxic niches.

摘要

缺氧诱导因子1α（HIF-1α）可促进癌细胞存活，是氧稳态的主要调节因子。缺氧与光子和碳离子辐射（碳离子）相结合可使HIF-1α稳定。在缺氧条件下沉默HIF-1α会导致头颈部鳞状细胞癌（HNSCC）细胞在接受光子和碳离子辐射后产生显著的放射增敏作用。因此，本研究旨在阐明HIF-1α在两种HNSCC细胞系及其癌症干细胞（CSC）亚群中对两种辐射的DNA双链断裂（DSB）检测、信号传导和修复过程中的潜在作用。在确认缺氧条件下HIF-1α在两种辐射暴露后的核穿梭现象后，我们发现，在非CSC和CSC中沉默HIF-1α会减少DSB检测的起始（P-ATM），并增加残留的磷酸化H2AX（γH2AX）病灶。虽然HIF-1α沉默并未调节53BP1表达，但P-DNA-PKcs（NHEJ-c）和RAD51（HR）信号减少。总之，我们的实验证明HIF-1α参与了DSB的检测和信号传导，也参与了主要的修复途径（NHEJ-c和HR），但并未偏向其中之一。因此，将HIF-1α沉默与两种类型的辐射相结合可能对靶向肿瘤低氧微环境中主要存在的CSC具有潜在的治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/42056818212e/cancers-13-03833-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/bfafd575b2cd/cancers-13-03833-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/ba7f4504e8a6/cancers-13-03833-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/be7d16c36576/cancers-13-03833-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/4febd935d152/cancers-13-03833-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/991416244075/cancers-13-03833-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/42056818212e/cancers-13-03833-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/bfafd575b2cd/cancers-13-03833-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/ba7f4504e8a6/cancers-13-03833-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/be7d16c36576/cancers-13-03833-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/4febd935d152/cancers-13-03833-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/991416244075/cancers-13-03833-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be83/8345054/42056818212e/cancers-13-03833-g006.jpg

相似文献

1
Involvement of HIF-1α in the Detection, Signaling, and Repair of DNA Double-Strand Breaks after Photon and Carbon-Ion Irradiation.缺氧诱导因子-1α在光子和碳离子照射后DNA双链断裂的检测、信号传导及修复中的作用
Cancers (Basel). 2021 Jul 30;13(15):3833. doi: 10.3390/cancers13153833.
2
Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells.缺氧对耐辐射头颈部鳞癌细胞光子和碳离子照射后双链断裂修复的影响。
Sci Rep. 2020 Dec 7;10(1):21357. doi: 10.1038/s41598-020-78354-7.
3
Differential pattern of HIF-1α expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect.碳离子或光子照射后HNSCC癌干细胞中HIF-1α表达的差异模式：氧效应的一种分子解释
Br J Cancer. 2017 May 9;116(10):1340-1349. doi: 10.1038/bjc.2017.100. Epub 2017 Apr 13.
4
The major DNA repair pathway after both proton and carbon-ion radiation is NHEJ, but the HR pathway is more relevant in carbon ions.在质子和碳离子辐射后，主要的 DNA 修复途径是 NHEJ，但 HR 途径在碳离子中更为相关。
Radiat Res. 2015 Mar;183(3):345-56. doi: 10.1667/RR13904.1. Epub 2015 Mar 4.
5
Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways.染料木黄酮通过抑制 DNA-PKcs 磷酸化，进而抑制非同源末端连接（NHEJ）和延迟同源重组（HR）修复途径，使脑胶质瘤细胞对碳离子敏感。
Radiother Oncol. 2018 Oct;129(1):84-94. doi: 10.1016/j.radonc.2018.04.005. Epub 2018 Apr 21.
6
Roles for 53BP1 in the repair of radiation-induced DNA double strand breaks.53BP1 在修复辐射诱导的 DNA 双链断裂中的作用。
DNA Repair (Amst). 2020 Sep;93:102915. doi: 10.1016/j.dnarep.2020.102915.
7
Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1 alpha-deficient mouse embryonic fibroblasts.DNA双链断裂修复受损导致缺氧诱导因子-1α缺陷型小鼠胚胎成纤维细胞产生化疗耐药性。
Carcinogenesis. 2008 Dec;29(12):2306-16. doi: 10.1093/carcin/bgn231. Epub 2008 Oct 8.
8
Carbon ion radiotherapy of human lung cancer attenuates HIF-1 signaling and acts with considerably enhanced therapeutic efficiency.碳离子放疗对人肺癌的治疗作用在于抑制 HIF-1 信号通路，从而显著提高治疗效果。
FASEB J. 2014 Mar;28(3):1412-21. doi: 10.1096/fj.13-242230. Epub 2013 Dec 17.
9
The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining.嘌呤骨架热休克蛋白90抑制剂PU-H71通过抑制同源重组和非同源末端连接的DNA修复，使癌细胞对重离子辐射敏感。
Radiother Oncol. 2016 Oct;121(1):162-168. doi: 10.1016/j.radonc.2016.08.029. Epub 2016 Sep 22.
10
Targeting of β1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells.靶向β1整合素会损害DNA修复，从而使头颈部癌细胞对放疗敏感。
Oncogene. 2016 Mar 17;35(11):1353-62. doi: 10.1038/onc.2015.212. Epub 2015 Jun 15.

引用本文的文献

1
Carbon ion irradiation mobilizes antitumor immunity: from concept to the clinic.碳离子辐射激发抗肿瘤免疫：从概念到临床
Radiat Oncol. 2025 May 22;20(1):85. doi: 10.1186/s13014-025-02647-2.
2
Photo-controlled co-delivery of verteporfin and acriflavine via platelets achieves potentiated glioblastoma-targeted photodynamic therapy.通过血小板实现的维替泊芬和吖啶黄的光控共递送可增强胶质母细胞瘤靶向光动力治疗。
J Nanobiotechnology. 2025 May 22;23(1):371. doi: 10.1186/s12951-025-03395-x.
3
Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.

本文引用的文献

1
Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter.肿瘤缺氧作为癌症治疗的障碍：水平为何重要。
Cancers (Basel). 2021 Jan 28;13(3):499. doi: 10.3390/cancers13030499.
2
Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells.缺氧对耐辐射头颈部鳞癌细胞光子和碳离子照射后双链断裂修复的影响。
Sci Rep. 2020 Dec 7;10(1):21357. doi: 10.1038/s41598-020-78354-7.
3
Hypoxia inducible factors in the tumor microenvironment as therapeutic targets of cancer stem cells.
糖酵解酶和代谢产物在肿瘤发生与治疗中调节DNA损伤修复的作用
Cell Commun Signal. 2025 Jan 23;23(1):44. doi: 10.1186/s12964-025-02047-9.
4
Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.缺氧与能量代谢重编程之间的反馈回路加剧了癌细胞的放射抗性。
Exp Hematol Oncol. 2024 May 22;13(1):55. doi: 10.1186/s40164-024-00519-1.
5
Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them?用于缺氧肿瘤的碳离子：我们是否充分利用了它们？
Cancers (Basel). 2023 Sep 9;15(18):4494. doi: 10.3390/cancers15184494.
6
Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.放疗前血清转铁蛋白水平对鼻咽癌患者放射敏感性和生存的预后价值
J Pers Med. 2023 Mar 13;13(3):511. doi: 10.3390/jpm13030511.
7
Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.靶向治疗诱导耐药中的肿瘤细胞可塑性：机制与新策略。
Signal Transduct Target Ther. 2023 Mar 11;8(1):113. doi: 10.1038/s41392-023-01383-x.
8
The 'stealth-bomber' paradigm for deciphering the tumour response to carbon-ion irradiation.解析碳离子照射肿瘤反应的“隐形轰炸机”范式。
Br J Cancer. 2023 Apr;128(8):1429-1438. doi: 10.1038/s41416-022-02117-6. Epub 2023 Jan 13.
9
Depletion of HIF-1α by Inducible Cre/loxP Increases the Sensitivity of Cultured Murine Hepatocytes to Ionizing Radiation in Hypoxia.缺氧条件下，通过诱导型 Cre/loxP 系统耗竭 HIF-1α 增加培养的鼠原代肝细胞对电离辐射的敏感性。
Cells. 2022 May 18;11(10):1671. doi: 10.3390/cells11101671.
10
Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts.线粒体在辐射反应中的作用：表观遗传、代谢和信号转导的影响。
Int J Mol Sci. 2021 Oct 13;22(20):11047. doi: 10.3390/ijms222011047.
肿瘤微环境中的缺氧诱导因子作为癌症干细胞的治疗靶点。
Life Sci. 2019 Nov 15;237:116952. doi: 10.1016/j.lfs.2019.116952. Epub 2019 Oct 14.
4
The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis.缺氧诱导因子-1α在晚期癌症幸存者中的预后价值：一项采用试验序贯分析的荟萃分析
Ther Adv Med Oncol. 2019 Sep 24;11:1758835919875851. doi: 10.1177/1758835919875851. eCollection 2019.
5
Knockdown of hypoxia-inducible factor-1 alpha by tumor targeted delivery of CRISPR/Cas9 system suppressed the metastasis of pancreatic cancer.肿瘤靶向递送 CRISPR/Cas9 系统敲低低氧诱导因子-1α 抑制胰腺癌转移。
J Control Release. 2019 Jun 28;304:204-215. doi: 10.1016/j.jconrel.2019.05.019. Epub 2019 May 14.
6
ROS Production and Distribution: A New Paradigm to Explain the Differential Effects of X-ray and Carbon Ion Irradiation on Cancer Stem Cell Migration and Invasion.活性氧的产生与分布：解释X射线和碳离子辐射对癌症干细胞迁移和侵袭产生不同影响的新范式。
Cancers (Basel). 2019 Apr 3;11(4):468. doi: 10.3390/cancers11040468.
7
Targeted Co-delivery of the Iron Chelator Deferoxamine and a HIF1α Inhibitor Impairs Pancreatic Tumor Growth.靶向递送铁螯合剂去铁胺和 HIF1α 抑制剂可抑制胰腺肿瘤生长。
ACS Nano. 2019 Feb 26;13(2):2176-2189. doi: 10.1021/acsnano.8b08823. Epub 2019 Jan 28.
8
Pharmacologic Targeting of Hypoxia-Inducible Factors.缺氧诱导因子的药物靶点
Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:379-403. doi: 10.1146/annurev-pharmtox-010818-021637.
9
Influence of Linear Energy Transfer on the Nucleo-shuttling of the ATM Protein: A Novel Biological Interpretation Relevant for Particles and Radiation.线性能量转移对 ATM 蛋白核穿梭的影响：与粒子和辐射相关的新生物学解释。
Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):709-718. doi: 10.1016/j.ijrobp.2018.10.011. Epub 2018 Oct 19.
10
Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their activities through Src and AMPK signaling pathways.严重缺氧会增加 ATM 和 DNA-PKcs 的表达，并通过Src 和 AMPK 信号通路增加它们的活性。
Biochem Biophys Res Commun. 2018 Oct 20;505(1):13-19. doi: 10.1016/j.bbrc.2018.09.068. Epub 2018 Sep 15.