• 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

三氧化二砷与依维莫司（RAD001）联合使用可协同诱导前列腺癌细胞发生自噬和凋亡。

Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells.

作者信息

Tai Sheng, Xu Lingfan, Xu Ming, Zhang Ligang, Zhang Yangyang, Zhang Kaipin, Zhang Li, Liang Chaozhao

机构信息

The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.

The Department of Urology, The Urological Institute of Anhui Medical University, China.

出版信息

Oncotarget. 2017 Feb 14;8(7):11206-11218. doi: 10.18632/oncotarget.14493.

DOI:10.18632/oncotarget.14493
PMID:28061438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5355258/
Abstract

The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2. Rad001 and ATO also can synergistically inhibit tumors in prostate cancer xenograft animal model. These results identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat prostate cancer.

摘要

PI3K-AKT-mTOR通路抑制剂，如Rad001，作为单一药物在前列腺癌中未显示出治疗效果。三氧化二砷可诱导前列腺癌细胞中的自噬途径。我们发现三氧化二砷可与Rad001协同诱导前列腺癌细胞的细胞毒性。此外，我们确定自噬和凋亡的协同诱导是其潜在机制。这种增强的自噬性细胞死亡伴随着Beclin1 mRNA稳定性的增加以及ATG5-ATG12共轭体、Beclin1和LC3-2的上调。Rad001和ATO在前列腺癌异种移植动物模型中也可协同抑制肿瘤。这些结果确定并验证了一种新机制，以增强和扩展现有的靶向治疗药物来治疗前列腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/059aa27cbfc5/oncotarget-08-11206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/0e7601098798/oncotarget-08-11206-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/a694a6eba334/oncotarget-08-11206-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/0406c1bf4cff/oncotarget-08-11206-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/9476249261cd/oncotarget-08-11206-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/7e5f837e7a86/oncotarget-08-11206-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/eac79d43e961/oncotarget-08-11206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/059aa27cbfc5/oncotarget-08-11206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/0e7601098798/oncotarget-08-11206-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/a694a6eba334/oncotarget-08-11206-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/0406c1bf4cff/oncotarget-08-11206-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/9476249261cd/oncotarget-08-11206-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/7e5f837e7a86/oncotarget-08-11206-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/eac79d43e961/oncotarget-08-11206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6323/5355258/059aa27cbfc5/oncotarget-08-11206-g007.jpg

相似文献

1
Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells.三氧化二砷与依维莫司（RAD001）联合使用可协同诱导前列腺癌细胞发生自噬和凋亡。
Oncotarget. 2017 Feb 14;8(7):11206-11218. doi: 10.18632/oncotarget.14493.
2
Arsenic trioxide synergizes with everolimus (Rad001) to induce cytotoxicity of ovarian cancer cells through increased autophagy and apoptosis.三氧化二砷与依维莫司（Rad001）协同作用，通过增加自噬和凋亡诱导卵巢癌细胞的细胞毒性。
Endocr Relat Cancer. 2012 Sep 21;19(5):711-23. doi: 10.1530/ERC-12-0150. Print 2012 Oct.
3
Combination of Rad001 (everolimus) and propachlor synergistically induces apoptosis through enhanced autophagy in prostate cancer cells.雷帕霉素（everolimus）与丙草胺联用通过增强自噬作用协同诱导前列腺癌细胞凋亡。
Mol Cancer Ther. 2012 Jun;11(6):1320-31. doi: 10.1158/1535-7163.MCT-11-0954. Epub 2012 Apr 5.
4
Arsenic trioxide induces autophagy and apoptosis in human glioma cells in vitro and in vivo through downregulation of survivin.三氧化二砷通过下调生存素诱导体外和体内人胶质瘤细胞自噬和凋亡。
J Mol Med (Berl). 2011 Sep;89(9):927-41. doi: 10.1007/s00109-011-0763-1. Epub 2011 May 19.
5
Arsenic trioxide induces programmed cell death through stimulation of ER stress and inhibition of the ubiquitin-proteasome system in human sarcoma cells.三氧化二砷通过刺激内质网应激和抑制泛素-蛋白酶体系统诱导人肉瘤细胞程序性死亡。
Cancer Lett. 2015 Jan 28;356(2 Pt B):762-72. doi: 10.1016/j.canlet.2014.10.025. Epub 2014 Oct 27.
6
Everolimus (RAD001) sensitizes prostate cancer cells to docetaxel by down-regulation of HIF-1α and sphingosine kinase 1.依维莫司（RAD001）通过下调缺氧诱导因子-1α（HIF-1α）和鞘氨醇激酶1使前列腺癌细胞对多西他赛敏感。
Oncotarget. 2016 Dec 6;7(49):80943-80956. doi: 10.18632/oncotarget.13115.
7
The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells: involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.RAD001 与 MK-2206 联合对 PTEN 突变型胃癌细胞具有协同细胞毒性作用：涉及 MAPK 依赖性自噬，但不涉及凋亡细胞死亡途径。
PLoS One. 2014 Jan 9;9(1):e85116. doi: 10.1371/journal.pone.0085116. eCollection 2014.
8
Impact of autophagy inhibition at different stages on cytotoxic effect of autophagy inducer in glioblastoma cells.不同阶段自噬抑制对胶质母细胞瘤细胞中自噬诱导剂细胞毒性作用的影响。
Cell Physiol Biochem. 2015;35(4):1303-16. doi: 10.1159/000373952. Epub 2015 Feb 11.
9
Antitumor effect of arsenic trioxide in human K562 and K562/ADM cells by autophagy.三氧化二砷通过自噬对人 K562 和 K562/ADM 细胞的抗肿瘤作用。
Toxicol Mech Methods. 2012 Sep;22(7):512-9. doi: 10.3109/15376516.2012.686534. Epub 2012 May 22.
10
Arsenic trioxide induces autophagy and antitumor effects in Burkitt's lymphoma Raji cells.三氧化二砷诱导伯基特淋巴瘤Raji细胞发生自噬并产生抗肿瘤作用。
Oncol Rep. 2014 Oct;32(4):1557-63. doi: 10.3892/or.2014.3369. Epub 2014 Jul 30.

引用本文的文献

1
The Effect of Arsenic Trioxide and Its Combination with Oxaliplatin and Docetaxel on the Induction of Autophagy and Expression of LC3 and Beclin-1 Genes in AGS and MKN-45 Gastric Cancer Cell Lines.三氧化二砷及其与奥沙利铂和多西他赛联合应用对AGS和MKN - 45胃癌细胞系自噬诱导及LC3和Beclin - 1基因表达的影响
Adv Pharm Bull. 2024 Dec 5;15(1):123-132. doi: 10.34172/apb.42747. eCollection 2025 Apr.
2
Predicting clinical response to everolimus in ER+ breast cancers using machine-learning.使用机器学习预测雌激素受体阳性乳腺癌患者对依维莫司的临床反应。
Front Mol Biosci. 2022 Oct 11;9:981962. doi: 10.3389/fmolb.2022.981962. eCollection 2022.
3

本文引用的文献

1
Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer.前列腺癌中雄激素剥夺治疗耐药的分子机制。
Oncotarget. 2016 Sep 27;7(39):64447-64470. doi: 10.18632/oncotarget.10901.
2
A comprehensive review of genomic landscape, biomarkers and treatment sequencing in castration-resistant prostate cancer.雄激素抵抗性前列腺癌的基因组图谱、生物标志物和治疗方案的综合综述。
Cancer Treat Rev. 2016 Jul;48:25-33. doi: 10.1016/j.ctrv.2016.06.005. Epub 2016 Jun 15.
3
Nut consumption and prostate cancer risk and mortality.
Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.
辛伐他汀和三氧化二砷通过下调 VEGF 和 OPN 异构体基因对前列腺癌细胞系的联合抗癌作用。
J Cell Mol Med. 2022 May;26(9):2728-2740. doi: 10.1111/jcmm.17286. Epub 2022 Apr 2.
4
The role of autophagy in metal-induced urogenital carcinogenesis.自噬在金属诱导的尿生殖系统致癌作用中的作用。
Semin Cancer Biol. 2021 Nov;76:247-257. doi: 10.1016/j.semcancer.2021.03.022. Epub 2021 Mar 30.
5
Mechanisms underlying the protective effect of tannic acid against arsenic trioxide‑induced cardiotoxicity in rats: Potential involvement of mitochondrial apoptosis.单宁酸对三氧化二砷诱导大鼠心脏毒性的保护作用机制：线粒体凋亡的潜在参与。
Mol Med Rep. 2020 Dec;22(6):4663-4674. doi: 10.3892/mmr.2020.11586. Epub 2020 Oct 11.
6
Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death.三氧化二砷与丙戊酸联合作用通过 G2/M 期阻滞和凋亡诱导有效抑制肺癌细胞生长。
Int J Mol Sci. 2020 Apr 10;21(7):2649. doi: 10.3390/ijms21072649.
7
Arsenic trioxide induces autophagic degradation of the FLT3-ITD mutated protein in FLT3-ITD acute myeloid leukemia cells.三氧化二砷诱导FLT3-ITD急性髓系白血病细胞中FLT3-ITD突变蛋白的自噬降解。
J Cancer. 2020 Mar 13;11(12):3476-3482. doi: 10.7150/jca.29751. eCollection 2020.
8
How Tumor Cells Choose Between Epithelial-Mesenchymal Transition and Autophagy to Resist Stress-Therapeutic Implications.肿瘤细胞如何在上皮-间质转化和自噬之间做出选择以抵抗应激——治疗意义
Front Pharmacol. 2018 Jul 2;9:714. doi: 10.3389/fphar.2018.00714. eCollection 2018.
9
PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis.PI3K/Akt/mTOR 信号通路与砷致癌的双向作用。
Mol Pharmacol. 2018 Jul;94(1):784-792. doi: 10.1124/mol.118.112268. Epub 2018 May 16.
10
Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells.三氧化二砷通过上调乳腺癌细胞中的 let-7a 抑制细胞生长和迁移。
Cell Cycle. 2017;16(24):2396-2403. doi: 10.1080/15384101.2017.1387699. Epub 2017 Nov 20.
食用坚果与前列腺癌风险及死亡率
Br J Cancer. 2016 Jul 26;115(3):371-4. doi: 10.1038/bjc.2016.181. Epub 2016 Jun 9.
4
Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer.TMPRSS2-ERG的存在与人类前列腺癌代谢谱的改变有关。
Oncotarget. 2016 Jul 5;7(27):42071-42085. doi: 10.18632/oncotarget.9817.
5
The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux.反向模式钠钙交换体1（NCX1）活性抑制剂KB-R7943通过激活JNK通路和阻断自噬流来促进前列腺癌细胞死亡。
Oncotarget. 2016 Jul 5;7(27):42059-42070. doi: 10.18632/oncotarget.9806.
6
Novel Gene Expression Signature Predictive of Clinical Recurrence After Radical Prostatectomy in Early Stage Prostate Cancer Patients.预测早期前列腺癌患者根治性前列腺切除术后临床复发的新型基因表达特征
Prostate. 2016 Oct;76(14):1239-56. doi: 10.1002/pros.23211. Epub 2016 Jun 8.
7
Cancer treatment and survivorship statistics, 2016.癌症治疗和生存统计，2016 年。
CA Cancer J Clin. 2016 Jul;66(4):271-89. doi: 10.3322/caac.21349. Epub 2016 Jun 2.
8
Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer: a systematic review.醋酸阿比特龙与恩杂鲁胺治疗转移性去势抵抗性前列腺癌的间接比较：一项系统评价
Asian J Androl. 2017 Mar-Apr;19(2):196-202. doi: 10.4103/1008-682X.178483.
9
The PI3K/AKT pathway in the pathogenesis of prostate cancer.前列腺癌发病机制中的 PI3K/AKT 通路。
Front Biosci (Landmark Ed). 2016 Jun 1;21(5):1084-91. doi: 10.2741/4443.
10
Effect of PI3K/Akt Signaling Pathway on the Process of Prostate Cancer Metastasis to Bone.PI3K/Akt信号通路对前列腺癌骨转移过程的影响
Cell Biochem Biophys. 2015 May;72(1):171-7. doi: 10.1007/s12013-014-0433-3.