• 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

人头颈癌细胞对谷胱甘肽和硫氧还蛋白代谢联合抑制的敏感性。

Susceptibility of human head and neck cancer cells to combined inhibition of glutathione and thioredoxin metabolism.

机构信息

Department of Pathology, The University of Iowa, Iowa City, Iowa, USA.

出版信息

PLoS One. 2012;7(10):e48175. doi: 10.1371/journal.pone.0048175. Epub 2012 Oct 31.

DOI:10.1371/journal.pone.0048175
PMID:23118946
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3485193/
Abstract

Increased glutathione (GSH) and thioredoxin (Trx) metabolism are mechanisms that are widely implicated in resistance of cancer cells to chemotherapy. The current study determined if simultaneous inhibition of GSH and Trx metabolism enhanced cell killing of human head and neck squamous cell carcinoma (HNSCC) cells by a mechanism involving oxidative stress. Inhibition of GSH and Trx metabolism with buthionine sulfoximine (BSO) and auranofin (AUR), respectively, induced significant decreases in clonogenic survival compared to either drug alone in FaDu, Cal-27 and SCC-25 HNSCC cells in vitro and in vivo in Cal-27 xenografts. BSO+AUR significantly increased glutathione and thioredoxin oxidation and suppressed peroxiredoxin activity in vitro. Pre-treatment with N-acetylcysteine completely reversed BSO+AUR-induced cell killing in FaDu and Cal-27 cells, while catalase and selenium supplementation only inhibited BSO+AUR-induced cell killing in FaDu cells. BSO+AUR decreased caspase 3/7 activity in HNSCC cells and significantly reduced the viability of both Bax/Bak double knockout (DKO) and DKO-Bax reconstituted hematopoietic cells suggesting that necrosis was involved. BSO+AUR also significantly sensitized FaDu, Cal-27, SCC-25 and SQ20B cells to cell killing induced by the EGFR inhibitor Erlotinib in vitro. These results support the conclusion that simultaneous inhibition of GSH and Trx metabolism pathways induces oxidative stress and clonogenic killing in HNSCCs and this strategy may be useful in sensitizing HNSCCs to EGFR inhibitors.

摘要

谷胱甘肽 (GSH) 和硫氧还蛋白 (Trx) 代谢的增加是广泛涉及癌细胞对化疗耐药的机制。本研究确定了同时抑制 GSH 和 Trx 代谢是否通过涉及氧化应激的机制增强了人头颈部鳞状细胞癌 (HNSCC) 细胞的细胞杀伤作用。用丁硫氨酸亚砜 (BSO) 和金诺芬 (AUR) 分别抑制 GSH 和 Trx 代谢，与单独使用任一药物相比，在 FaDu、Cal-27 和 SCC-25 HNSCC 细胞的体外和 Cal-27 异种移植物的体内均显著降低了集落形成存活。BSO+AUR 显著增加了谷胱甘肽和硫氧还蛋白的氧化，并抑制了体外过氧化物酶的活性。用 N-乙酰半胱氨酸预处理完全逆转了 BSO+AUR 诱导的 FaDu 和 Cal-27 细胞的细胞杀伤作用，而过氧化氢酶和硒补充仅抑制了 BSO+AUR 诱导的 FaDu 细胞的细胞杀伤作用。BSO+AUR 降低了 HNSCC 细胞中 caspase 3/7 的活性，并显著降低了 Bax/Bak 双敲除 (DKO) 和 DKO-Bax 重建的造血细胞的活力，表明坏死参与其中。BSO+AUR 还显著增强了 FaDu、Cal-27、SCC-25 和 SQ20B 细胞对表皮生长因子受体抑制剂 Erlotinib 在体外诱导的细胞杀伤作用的敏感性。这些结果支持以下结论：同时抑制 GSH 和 Trx 代谢途径会诱导 HNSCC 中的氧化应激和集落杀伤作用，这种策略可能有助于增强 HNSCC 对表皮生长因子受体抑制剂的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/46f2df2bc64d/pone.0048175.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/0cf01854a845/pone.0048175.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/8489131e50b7/pone.0048175.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/0e834b24dec7/pone.0048175.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/839156284f03/pone.0048175.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/dfcf6a6acc82/pone.0048175.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/e0b4ce8efcd3/pone.0048175.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/f307ba347792/pone.0048175.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/41d9c89e2f50/pone.0048175.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/d474c82ec388/pone.0048175.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/46f2df2bc64d/pone.0048175.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/0cf01854a845/pone.0048175.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/8489131e50b7/pone.0048175.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/0e834b24dec7/pone.0048175.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/839156284f03/pone.0048175.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/dfcf6a6acc82/pone.0048175.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/e0b4ce8efcd3/pone.0048175.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/f307ba347792/pone.0048175.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/41d9c89e2f50/pone.0048175.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/d474c82ec388/pone.0048175.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/3485193/46f2df2bc64d/pone.0048175.g010.jpg

相似文献

1
Susceptibility of human head and neck cancer cells to combined inhibition of glutathione and thioredoxin metabolism.人头颈癌细胞对谷胱甘肽和硫氧还蛋白代谢联合抑制的敏感性。
PLoS One. 2012;7(10):e48175. doi: 10.1371/journal.pone.0048175. Epub 2012 Oct 31.
2
Targeting redox homeostasis in rhabdomyosarcoma cells: GSH-depleting agents enhance auranofin-induced cell death.靶向横纹肌肉瘤细胞的氧化还原稳态：耗竭 GSH 的试剂增强金诺芬诱导的细胞死亡。
Cell Death Dis. 2017 Oct 5;8(10):e3067. doi: 10.1038/cddis.2017.412.
3
Inhibition of glutathione and thioredoxin metabolism enhances sensitivity to perifosine in head and neck cancer cells.抑制谷胱甘肽和硫氧还蛋白代谢可增强头颈癌细胞对帕比司他的敏感性。
J Oncol. 2009;2009:519563. doi: 10.1155/2009/519563. Epub 2009 Sep 2.
4
Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.靶向治疗头颈部癌症中的谷胱甘肽、硫氧还蛋白和 Nrf2 抗氧化系统。
Antioxid Redox Signal. 2017 Jul 10;27(2):106-114. doi: 10.1089/ars.2016.6841. Epub 2016 Nov 14.
5
Enhancement of Radiation Response in Breast Cancer Stem Cells by Inhibition of Thioredoxin- and Glutathione-Dependent Metabolism.通过抑制硫氧还蛋白和谷胱甘肽依赖性代谢增强乳腺癌干细胞的辐射反应
Radiat Res. 2016 Oct;186(4):385-395. doi: 10.1667/RR14463.1. Epub 2016 Sep 19.
6
Simultaneous inhibition of glutathione- and thioredoxin-dependent metabolism is necessary to potentiate 17AAG-induced cancer cell killing via oxidative stress.同时抑制谷胱甘肽和硫氧还蛋白依赖性代谢对于通过氧化应激增强 17AAG 诱导的癌细胞杀伤是必要的。
Free Radic Biol Med. 2012 Jan 15;52(2):436-43. doi: 10.1016/j.freeradbiomed.2011.10.493. Epub 2011 Nov 4.
7
Dual targeting of the thioredoxin and glutathione antioxidant systems in malignant B cells: a novel synergistic therapeutic approach.恶性B细胞中硫氧还蛋白和谷胱甘肽抗氧化系统的双重靶向：一种新型协同治疗方法。
Exp Hematol. 2015 Feb;43(2):89-99. doi: 10.1016/j.exphem.2014.10.004. Epub 2014 Oct 22.
8
Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism.同时破坏谷胱甘肽和硫氧还蛋白代谢增强卡铂介导的肺癌细胞杀伤作用。
Clin Cancer Res. 2011 Oct 1;17(19):6206-17. doi: 10.1158/1078-0432.CCR-11-0736. Epub 2011 Aug 15.
9
2-Deoxy-D-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells.2-脱氧-D-葡萄糖与顺铂联合通过代谢性氧化应激增强人头颈癌细胞的细胞毒性。
Cancer Res. 2007 Apr 1;67(7):3364-70. doi: 10.1158/0008-5472.CAN-06-3717.
10
Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia.硫氧还蛋白-1氧化还原信号传导调节细胞对高氧的存活反应。
Free Radic Biol Med. 2014 Oct;75:167-77. doi: 10.1016/j.freeradbiomed.2014.07.023. Epub 2014 Aug 6.

引用本文的文献

1
The gold complex auranofin sensitizes platinum resistant epithelial ovarian cancer cells to cisplatin.金络合物金诺芬可使铂耐药的上皮性卵巢癌细胞对顺铂敏感。
Biochem Biophys Rep. 2025 Mar 29;42:101996. doi: 10.1016/j.bbrep.2025.101996. eCollection 2025 Jun.
2
Mitoregulin Promotes Cell Cycle Progression in Non-Small Cell Lung Cancer Cells.线粒体调节蛋白促进非小细胞肺癌细胞的细胞周期进程。
Int J Mol Sci. 2025 Feb 24;26(5):1939. doi: 10.3390/ijms26051939.
3
The disruption of NEAT1-miR-125b-5p-SLC1A5 cascade defines the oncogenicity and differential immune profile in head and neck squamous cell carcinoma.

本文引用的文献

1
Simultaneous inhibition of glutathione- and thioredoxin-dependent metabolism is necessary to potentiate 17AAG-induced cancer cell killing via oxidative stress.同时抑制谷胱甘肽和硫氧还蛋白依赖性代谢对于通过氧化应激增强 17AAG 诱导的癌细胞杀伤是必要的。
Free Radic Biol Med. 2012 Jan 15;52(2):436-43. doi: 10.1016/j.freeradbiomed.2011.10.493. Epub 2011 Nov 4.
2
Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism.同时破坏谷胱甘肽和硫氧还蛋白代谢增强卡铂介导的肺癌细胞杀伤作用。
Clin Cancer Res. 2011 Oct 1;17(19):6206-17. doi: 10.1158/1078-0432.CCR-11-0736. Epub 2011 Aug 15.
3
NEAT1- miR-125b-5p-SLC1A5级联反应的破坏定义了头颈部鳞状细胞癌的致癌性和差异免疫特征。
Cell Death Discov. 2024 Sep 3;10(1):392. doi: 10.1038/s41420-024-02158-1.
4
Carrying Temoporfin with Human Serum Albumin: A New Perspective for Photodynamic Application in Head and Neck Cancer.携载替莫泊芬与人血清白蛋白：头颈癌光动力应用的新视角。
Biomolecules. 2022 Dec 29;13(1):68. doi: 10.3390/biom13010068.
5
Optimization of the Solvent and In Vivo Administration Route of Auranofin in a Syngeneic Non-Small Cell Lung Cancer and Glioblastoma Mouse Model.金诺芬在同基因非小细胞肺癌和胶质母细胞瘤小鼠模型中的溶剂及体内给药途径优化
Pharmaceutics. 2022 Dec 9;14(12):2761. doi: 10.3390/pharmaceutics14122761.
6
Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines.谷胱甘肽水平与急性淋巴细胞白血病细胞系中的甲氨蝶呤耐药性相关。
Front Oncol. 2022 Dec 1;12:1032336. doi: 10.3389/fonc.2022.1032336. eCollection 2022.
7
The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance.硫氧还蛋白解毒系统在癌症进展和耐药性中的作用
Front Mol Biosci. 2022 May 19;9:883297. doi: 10.3389/fmolb.2022.883297. eCollection 2022.
8
Positive Aspects of Oxidative Stress at Different Levels of the Human Body: A Review.人体不同层面氧化应激的积极方面：综述
Antioxidants (Basel). 2022 Mar 17;11(3):572. doi: 10.3390/antiox11030572.
9
The gold complex auranofin: new perspectives for cancer therapy.金络合物金诺芬：癌症治疗的新视角。
Discov Oncol. 2021 Oct 20;12(1):42. doi: 10.1007/s12672-021-00439-0.
10
Hypoxic Transformation of Immune Cell Metabolism Within the Microenvironment of Oral Cancers.口腔癌微环境中免疫细胞代谢的缺氧转变
Front Oral Health. 2020 Dec 16;1:585710. doi: 10.3389/froh.2020.585710. eCollection 2020.
Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: Implications for development of specific inhibitors.
人细胞质和线粒体硫氧还蛋白还原酶的底物和抑制剂特异性不同：对特异性抑制剂开发的影响。
Free Radic Biol Med. 2011 Mar 15;50(6):689-99. doi: 10.1016/j.freeradbiomed.2010.12.015. Epub 2010 Dec 21.
4
Loss of thioredoxin reductase 1 renders tumors highly susceptible to pharmacologic glutathione deprivation.硫氧还蛋白还原酶 1 的缺失使肿瘤对药物诱导的谷胱甘肽耗竭非常敏感。
Cancer Res. 2010 Nov 15;70(22):9505-14. doi: 10.1158/0008-5472.CAN-10-1509. Epub 2010 Nov 2.
5
Gamma-glutamyltransferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting.癌细胞中的γ-谷氨酰转移酶处于肿瘤进展、耐药性和药物靶向的交汇点。
Anticancer Res. 2010 Apr;30(4):1169-81.
6
Mitochondrial respiratory chain involvement in peroxiredoxin 3 oxidation by phenethyl isothiocyanate and auranofin.苯乙基异硫氰酸酯和金诺芬诱导过氧化物酶 3 氧化与线粒体呼吸链的关系。
FEBS Lett. 2010 Mar 19;584(6):1257-62. doi: 10.1016/j.febslet.2010.02.042. Epub 2010 Feb 19.
7
The thioredoxin-thioredoxin reductase system can function in vivo as an alternative system to reduce oxidized glutathione in Saccharomyces cerevisiae.硫氧还蛋白-硫氧还蛋白还原酶系统可以在体内作为酿酒酵母中还原氧化型谷胱甘肽的替代系统发挥作用。
J Biol Chem. 2010 Feb 26;285(9):6118-26. doi: 10.1074/jbc.M109.062844. Epub 2009 Dec 1.
8
High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy.高水平的硫氧还蛋白还原酶 1 调节药物特异性细胞毒性功效。
Free Radic Biol Med. 2009 Dec 1;47(11):1661-71. doi: 10.1016/j.freeradbiomed.2009.09.016. Epub 2009 Sep 17.
9
Inhibition of glutathione and thioredoxin metabolism enhances sensitivity to perifosine in head and neck cancer cells.抑制谷胱甘肽和硫氧还蛋白代谢可增强头颈癌细胞对帕比司他的敏感性。
J Oncol. 2009;2009:519563. doi: 10.1155/2009/519563. Epub 2009 Sep 2.
10
The NADPH-dependent thioredoxin system constitutes a functional backup for cytosolic glutathione reductase in Arabidopsis.依赖于NADPH的硫氧还蛋白系统是拟南芥胞质谷胱甘肽还原酶的功能备份。
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9109-14. doi: 10.1073/pnas.0900206106. Epub 2009 May 18.