• 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

来曲替尼通过 CHOP 依赖性 DR5 诱导增强 TRAIL 诱导的胶质瘤细胞凋亡。

Lestaurtinib potentiates TRAIL-induced apoptosis in glioma via CHOP-dependent DR5 induction.

机构信息

Department of Neurosurgery, Xingtai People's Hospital, Xingtai, China.

Department of Operating Room, Xingtai People's Hospital, Xingtai, China.

出版信息

J Cell Mol Med. 2020 Jul;24(14):7829-7840. doi: 10.1111/jcmm.15415. Epub 2020 May 22.

DOI:10.1111/jcmm.15415
PMID:32441887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7348155/
Abstract

Lestaurtinib, also called CEP-701, is an inhibitor of tyrosine kinase, causes haematological remission in patients with AML possessing FLT3-ITD (FLT3 gene) internal tandem duplication and strongly inhibits tyrosine kinase FLT3. Treatment with lestaurtinib modulates various signalling pathways and leads to cell growth arrest and programmed cell death in several tumour types. However, the effect of lestaurtinib on glioma remains unclear. In this study, we examined lestaurtinib and TRAIL interactions in glioma cells and observed their synergistic activity on glioma cell apoptosis. While U87 and U251 cells showed resistance to TRAIL single treatment, they were sensitized to apoptosis induced by TRAIL in the presence of lestaurtinib because of increased death receptor 5 (DR5) levels through CHOP-dependent manner. We also demonstrated using a xenograft model of mouse that the tumour growth was absolutely suppressed because of the combined treatment compared to TRAIL or lestaurtinib treatment carried out singly. Our findings reveal a potential new strategy to improve antitumour activity induced by TRAIL in glioma cells using lestaurtinib through a mechanism dependent on CHOP.

摘要

lestaurtinib，也称为CEP-701，是一种酪氨酸激酶抑制剂，可导致 AML 患者血液学缓解，这些患者具有 FLT3-ITD（FLT3 基因）内部串联重复，并强烈抑制酪氨酸激酶 FLT3。lestaurtinib 的治疗可调节多种信号通路，并导致多种肿瘤类型的细胞生长停滞和程序性细胞死亡。然而，lestaurtinib 对神经胶质瘤的影响尚不清楚。在这项研究中，我们研究了 lestaurtinib 和 TRAIL 在神经胶质瘤细胞中的相互作用，并观察了它们在神经胶质瘤细胞凋亡中的协同作用。虽然 U87 和 U251 细胞对 TRAIL 单一治疗具有抗性，但由于通过 CHOP 依赖性方式增加了死亡受体 5（DR5）水平，它们对 lestaurtinib 存在下 TRAIL 诱导的细胞凋亡变得敏感。我们还使用了小鼠异种移植模型证明，与单独进行 TRAIL 或 lestaurtinib 治疗相比，联合治疗可完全抑制肿瘤生长。我们的研究结果揭示了一种潜在的新策略，通过依赖于 CHOP 的机制，使用 lestaurtinib 提高 TRAIL 在神经胶质瘤细胞中诱导的抗肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/81c22836788a/JCMM-24-7829-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/5bbcd4df6351/JCMM-24-7829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/5508826d4c9b/JCMM-24-7829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/cf6be8c5f52b/JCMM-24-7829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/d29e655f5826/JCMM-24-7829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/da4294c64a58/JCMM-24-7829-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/81c22836788a/JCMM-24-7829-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/5bbcd4df6351/JCMM-24-7829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/5508826d4c9b/JCMM-24-7829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/cf6be8c5f52b/JCMM-24-7829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/d29e655f5826/JCMM-24-7829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/da4294c64a58/JCMM-24-7829-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/983a/7348155/81c22836788a/JCMM-24-7829-g006.jpg

相似文献

1
Lestaurtinib potentiates TRAIL-induced apoptosis in glioma via CHOP-dependent DR5 induction.来曲替尼通过 CHOP 依赖性 DR5 诱导增强 TRAIL 诱导的胶质瘤细胞凋亡。
J Cell Mol Med. 2020 Jul;24(14):7829-7840. doi: 10.1111/jcmm.15415. Epub 2020 May 22.
2
Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation.胺碘酮通过 CHOP 介导的 DR5 上调使人类神经胶质瘤细胞而非星形胶质细胞对 TRAIL 诱导的凋亡敏感。
Neuro Oncol. 2011 Mar;13(3):267-79. doi: 10.1093/neuonc/noq195. Epub 2011 Feb 3.
3
Arsenic trioxide sensitizes human glioma cells, but not normal astrocytes, to TRAIL-induced apoptosis via CCAAT/enhancer-binding protein homologous protein-dependent DR5 up-regulation.三氧化二砷通过CCAAT/增强子结合蛋白同源蛋白依赖性上调死亡受体5，使人类胶质瘤细胞而非正常星形胶质细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的凋亡敏感。
Cancer Res. 2008 Jan 1;68(1):266-75. doi: 10.1158/0008-5472.CAN-07-2444.
4
Verrucarin A sensitizes TRAIL-induced apoptosis via the upregulation of DR5 in an eIF2α/CHOP-dependent manner.疣菌素 A 通过上调 DR5 以 eIF2α/CHOP 依赖的方式敏感化 TRAIL 诱导的细胞凋亡。
Toxicol In Vitro. 2013 Feb;27(1):257-63. doi: 10.1016/j.tiv.2012.09.001. Epub 2012 Sep 12.
5
Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells.韦诺地洛尔增强肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的弥漫性大B细胞淋巴瘤细胞凋亡。
Mol Carcinog. 2017 Oct;56(10):2190-2199. doi: 10.1002/mc.22672. Epub 2017 May 15.
6
Upregulation of DR5 by proteasome inhibitors potently sensitizes glioma cells to TRAIL-induced apoptosis.蛋白酶体抑制剂上调DR5可有效使胶质瘤细胞对TRAIL诱导的凋亡敏感。
FEBS J. 2008 Apr;275(8):1925-36. doi: 10.1111/j.1742-4658.2008.06351.x. Epub 2008 Mar 13.
7
Tanshinone IIA Facilitates TRAIL Sensitization by Up-regulating DR5 through the ROS-JNK-CHOP Signaling Axis in Human Ovarian Carcinoma Cell Lines.丹参酮IIA通过ROS-JNK-CHOP信号轴上调DR5促进人卵巢癌细胞系对TRAIL的敏感性。
Chem Res Toxicol. 2015 Aug 17;28(8):1574-83. doi: 10.1021/acs.chemrestox.5b00150. Epub 2015 Jul 31.
8
Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner.芹菜素通过以p53依赖的方式上调DR4/DR5表达来增强非小细胞肺癌的TRAIL治疗效果。
Sci Rep. 2016 Oct 18;6:35468. doi: 10.1038/srep35468.
9
Azadirone, a limonoid tetranortriterpene, induces death receptors and sensitizes human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through a p53 protein-independent mechanism: evidence for the role of the ROS-ERK-CHOP-death receptor pathway.azadirone，一种柠檬苦素四环三萜，通过一种不依赖 p53 蛋白的机制诱导死亡受体，并使人类癌细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）敏感：证据表明该机制涉及 ROS-ERK-CHOP-死亡受体途径。
J Biol Chem. 2013 Nov 8;288(45):32343-32356. doi: 10.1074/jbc.M113.455188. Epub 2013 Sep 27.
10
Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation.辣椒素通过上调 DR5 和下调 survivin 使恶性神经胶质瘤细胞对 TRAIL 介导的细胞凋亡敏感。
Carcinogenesis. 2010 Mar;31(3):367-75. doi: 10.1093/carcin/bgp298. Epub 2009 Nov 25.

引用本文的文献

1
Retraction Note: Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer.撤稿说明：库潘尼西通过调节结直肠癌中的AKT/FoxO3a/PUMA轴促进生长抑制和细胞凋亡。
Cell Death Dis. 2025 Apr 29;16(1):352. doi: 10.1038/s41419-025-07679-w.
2
MDM2 inhibitor induces apoptosis in colon cancer cells through activation of the CHOP-DR5 pathway, independent of p53 phenotype.MDM2抑制剂通过激活CHOP-DR5途径诱导结肠癌细胞凋亡，与p53表型无关。
Front Pharmacol. 2025 Apr 8;16:1508421. doi: 10.3389/fphar.2025.1508421. eCollection 2025.
3
Gene Expression Profiling Regulated by lncRNA H19 Using Bioinformatic Analyses in Glioma Cell Lines.

本文引用的文献

1
Comprehensive Analysis of ERK1/2 Substrates for Potential Combination Immunotherapies.ERK1/2 底物的综合分析及其在潜在联合免疫治疗中的应用。
Trends Pharmacol Sci. 2019 Nov;40(11):897-910. doi: 10.1016/j.tips.2019.09.005. Epub 2019 Oct 29.
2
Tumor necrosis factor related apoptosis inducing ligand (TRAIL) regulates deubiquitinase USP5 in tumor cells.肿瘤坏死因子相关凋亡诱导配体（TRAIL）在肿瘤细胞中调节去泛素化酶USP5。
Oncotarget. 2019 Oct 8;10(56):5745-5754. doi: 10.18632/oncotarget.27196.
3
Past, Current, and Future of Immunotherapies for Prostate Cancer.
利用生物信息学分析探讨 lncRNA H19 调控脑胶质瘤细胞系基因表达谱
Cancer Genomics Proteomics. 2024 Nov-Dec;21(6):608-621. doi: 10.21873/cgp.20477.
4
Application of calcium overload-based ion interference therapy in tumor treatment: strategies, outcomes, and prospects.基于钙超载的离子干扰疗法在肿瘤治疗中的应用：策略、成果与展望。
Front Pharmacol. 2024 Feb 15;15:1352377. doi: 10.3389/fphar.2024.1352377. eCollection 2024.
5
ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy.ASPP2通过抑制自噬促进宫颈癌细胞凋亡。
Exp Ther Med. 2022 Oct 20;24(6):726. doi: 10.3892/etm.2022.11662. eCollection 2022 Dec.
6
Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress.比辛通过激活 AMPK 的内质网应激预防结直肠癌发生。
Biomed Res Int. 2022 Feb 24;2022:9329151. doi: 10.1155/2022/9329151. eCollection 2022.
前列腺癌免疫疗法的过去、现状与未来
Front Oncol. 2019 Sep 11;9:884. doi: 10.3389/fonc.2019.00884. eCollection 2019.
4
Current promising treatment strategy for glioblastoma multiform: A review.多形性胶质母细胞瘤当前有前景的治疗策略：综述
Oncol Rev. 2019 Jul 25;13(2):417. doi: 10.4081/oncol.2019.417. eCollection 2019 Jul 22.
5
Genetic and molecular epidemiology of adult diffuse glioma.成人弥漫性神经胶质瘤的遗传和分子流行病学。
Nat Rev Neurol. 2019 Jul;15(7):405-417. doi: 10.1038/s41582-019-0220-2. Epub 2019 Jun 21.
6
Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer.乳腺癌中 CDK4/6 抑制剂策略及联合治疗的最新进展。
Cells. 2019 Apr 6;8(4):321. doi: 10.3390/cells8040321.
7
Mechanisms of Anticancer Drug Resistance in Hepatoblastoma.肝母细胞瘤中抗癌药物耐药的机制
Cancers (Basel). 2019 Mar 22;11(3):407. doi: 10.3390/cancers11030407.
8
Current State of Immunotherapy for Treatment of Glioblastoma.免疫疗法治疗胶质母细胞瘤的现状。
Curr Treat Options Oncol. 2019 Feb 21;20(3):24. doi: 10.1007/s11864-019-0619-4.
9
Phase II trial of Lestaurtinib, a JAK2 inhibitor, in patients with myelofibrosis.JAK2抑制剂来他替尼治疗骨髓纤维化患者的II期试验。
Leuk Lymphoma. 2019 May;60(5):1343-1345. doi: 10.1080/10428194.2018.1532509. Epub 2019 Jan 22.
10
The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection.C/EBP 同源蛋白（CHOP）转录因子在内质网应激诱导的细胞凋亡和微生物感染中发挥作用。
Front Immunol. 2019 Jan 4;9:3083. doi: 10.3389/fimmu.2018.03083. eCollection 2018.