• 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

斑蝥素通过消耗慢性髓性白血病中的BCR-ABL克服伊马替尼耐药性。

Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia.

作者信息

Sun Xiaoyan, Cai Xueting, Yang Jie, Chen Jiao, Guo Caixia, Cao Peng

机构信息

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.

Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu, China.

出版信息

Mol Cells. 2016 Dec;39(12):869-876. doi: 10.14348/molcells.2016.0023. Epub 2016 Dec 13.

DOI:10.14348/molcells.2016.0023
PMID:27989101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5223104/
Abstract

Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells. CTD induced cell cycle arrest at mitotic phase and triggered DNA damage in CML cells. The ATM/ATR inhibitor CGK733 abrogated CTD-induced mitotic arrest but promoted the cytotoxic effects of CTD. In addition, we demonstrated that CTD downregulated the expression of the BCR-ABL protein and suppressed its downstream signal transduction. Real-time quantitative PCR revealed that CTD inhibited BCR-ABL at transcriptional level. Knockdown of BCR-ABL increased the cell-killing effects of CTD in K562 cells. These findings indicated that CTD overcomes imatinib resistance through depletion of BCR-ABL. Taken together, CTD is an important new candidate agent for CML therapy.

摘要

斑蝥素（CTD）是从传统中药斑蝥中分离出的一种活性化合物，对多种癌细胞具有抗癌特性。然而，其对人类慢性髓性白血病（CML）细胞，包括对伊马替尼耐药的CML细胞的作用却知之甚少。本研究的目的是探讨CTD是否能克服伊马替尼耐药CML细胞中的伊马替尼耐药性，并探索与该作用相关的潜在机制。我们的结果表明，CTD强烈抑制伊马替尼敏感和伊马替尼耐药的CML细胞的生长。CTD诱导CML细胞在有丝分裂期发生细胞周期阻滞并引发DNA损伤。ATM/ATR抑制剂CGK733消除了CTD诱导的有丝分裂阻滞，但增强了CTD的细胞毒性作用。此外，我们证明CTD下调BCR-ABL蛋白的表达并抑制其下游信号转导。实时定量PCR显示CTD在转录水平抑制BCR-ABL。敲低BCR-ABL增强了CTD对K562细胞的杀伤作用。这些发现表明CTD通过消耗BCR-ABL克服伊马替尼耐药性。综上所述，CTD是CML治疗的一种重要新型候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/74e439e9bf48/molce-39-12-869f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/a2293d5ff4fc/molce-39-12-869f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/7d1eaf9a03a2/molce-39-12-869f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/266e03b3dabd/molce-39-12-869f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/f001a9e77264/molce-39-12-869f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/3157fc0d3bc4/molce-39-12-869f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/74e439e9bf48/molce-39-12-869f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/a2293d5ff4fc/molce-39-12-869f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/7d1eaf9a03a2/molce-39-12-869f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/266e03b3dabd/molce-39-12-869f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/f001a9e77264/molce-39-12-869f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/3157fc0d3bc4/molce-39-12-869f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5269/5223104/74e439e9bf48/molce-39-12-869f6.jpg

相似文献

1
Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia.斑蝥素通过消耗慢性髓性白血病中的BCR-ABL克服伊马替尼耐药性。
Mol Cells. 2016 Dec;39(12):869-876. doi: 10.14348/molcells.2016.0023. Epub 2016 Dec 13.
2
JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia.JKST6，一种新型 BCR-ABL1/STAT5 信号通路的多激酶调节剂，可增强直接 BCR-ABL1 抑制作用，并克服慢性髓性白血病中的伊马替尼耐药性。
Biomed Pharmacother. 2021 Dec;144:112330. doi: 10.1016/j.biopha.2021.112330. Epub 2021 Oct 19.
3
A novel tubulin polymerization inhibitor, MPT0B206, downregulates Bcr-Abl expression and induces apoptosis in imatinib-sensitive and imatinib-resistant CML cells.一种新型微管蛋白聚合抑制剂 MPT0B206 下调 Bcr-Abl 表达并诱导伊马替尼敏感和耐药 CML 细胞凋亡。
Apoptosis. 2016 Sep;21(9):1008-18. doi: 10.1007/s10495-016-1264-z.
4
A novel HDAC inhibitor chidamide combined with imatinib synergistically targets tyrosine kinase inhibitor resistant chronic myeloid leukemia cells.新型组蛋白去乙酰化酶抑制剂西达本胺联合伊马替尼协同靶向治疗酪氨酸激酶抑制剂耐药慢性髓系白血病细胞。
Biomed Pharmacother. 2020 Sep;129:110390. doi: 10.1016/j.biopha.2020.110390. Epub 2020 Jun 17.
5
Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia.靶向刺猬信号通路和自噬可克服BCR-ABL阳性慢性髓性白血病的耐药性。
Autophagy. 2015;11(2):355-72. doi: 10.4161/15548627.2014.994368.
6
Novel HDAC inhibitor MAKV-8 and imatinib synergistically kill chronic myeloid leukemia cells via inhibition of BCR-ABL/MYC-signaling: effect on imatinib resistance and stem cells.新型 HDAC 抑制剂 MAKV-8 与伊马替尼协同抑制 BCR-ABL/MYC 信号通路杀伤慢性髓系白血病细胞：对伊马替尼耐药和干细胞的影响。
Clin Epigenetics. 2020 May 19;12(1):69. doi: 10.1186/s13148-020-00839-z.
7
MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.新型抗微管蛋白药物MPT0B169抑制非耐药和伊马替尼耐药的慢性髓性白血病细胞中的Bcr-Abl表达并诱导线粒体介导的凋亡。
PLoS One. 2016 Jan 27;11(1):e0148093. doi: 10.1371/journal.pone.0148093. eCollection 2016.
8
Blockade of the interaction between Bcr-Abl and PTB1B by small molecule SBF-1 to overcome imatinib-resistance of chronic myeloid leukemia cells.小分子SBF-1阻断Bcr-Abl与PTB1B之间的相互作用以克服慢性髓性白血病细胞的伊马替尼耐药性。
Cancer Lett. 2016 Mar 1;372(1):82-8. doi: 10.1016/j.canlet.2015.12.014. Epub 2015 Dec 22.
9
Imatinib mesylate induces cisplatin hypersensitivity in Bcr-Abl+ cells by differential modulation of p53 transcriptional and proapoptotic activity.甲磺酸伊马替尼通过差异调节 p53 转录和促凋亡活性诱导 Bcr-Abl+细胞对顺铂的敏感性。
Cancer Res. 2009 Dec 15;69(24):9337-45. doi: 10.1158/0008-5472.CAN-09-0548.
10
Simvastatin potentiates the cell-killing activity of imatinib in imatinib-resistant chronic myeloid leukemia cells mainly through PI3K/AKT pathway attenuation and Myc downregulation.辛伐他汀通过抑制 PI3K/AKT 通路和下调 Myc 表达增强伊马替尼耐药慢性髓系白血病细胞的细胞杀伤活性。
Eur J Pharmacol. 2021 Dec 15;913:174633. doi: 10.1016/j.ejphar.2021.174633. Epub 2021 Nov 27.

引用本文的文献

1
Gut microbial changes in a specialist blister beetle larvae and their nutritional metabolic characteristics.一种专业斑蝥幼虫的肠道微生物变化及其营养代谢特征。
Ecol Evol. 2024 Aug 22;14(8):e70184. doi: 10.1002/ece3.70184. eCollection 2024 Aug.
2
Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.斑蝥素的肝毒性机制：治疗干预的见解与策略
Front Pharmacol. 2023 Jun 13;14:1201404. doi: 10.3389/fphar.2023.1201404. eCollection 2023.
3
Pharmacological mechanism of mylabris in the treatment of leukemia based on bioinformatics and systematic pharmacology.

本文引用的文献

1
Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.斑蝥素对A431人皮肤癌（表皮样癌）细胞的体内外抗癌作用。
Environ Toxicol. 2017 Mar;32(3):723-738. doi: 10.1002/tox.22273. Epub 2016 Apr 25.
2
PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21.PP2A抑制剂通过JNK/Sp1依赖的细胞周期蛋白依赖性激酶1（CDK1）下调和自噬依赖的p21上调来阻止G2/M期转换。
Oncotarget. 2015 Jul 30;6(21):18469-83. doi: 10.18632/oncotarget.4063.
3
Cantharidin Induces Apoptosis Through the Calcium/PKC-Regulated Endoplasmic Reticulum Stress Pathway in Human Bladder Cancer Cells.
基于生物信息学和系统药理学的斑蝥治疗白血病的作用机制。
Bioengineered. 2021 Dec;12(1):3229-3239. doi: 10.1080/21655979.2021.1943110.
4
Antitumor potential of the protein phosphatase inhibitor, cantharidin, and selected derivatives.蛋白磷酸酶抑制剂斑蝥素及其衍生物的抗肿瘤潜力。
Bioorg Med Chem. 2021 Feb 15;32:116012. doi: 10.1016/j.bmc.2021.116012. Epub 2021 Jan 9.
5
Cantharidin Induces Apoptosis and Promotes Differentiation of AML Cells Through Nuclear Receptor Nur77-Mediated Signaling Pathway.斑蝥素通过核受体Nur77介导的信号通路诱导急性髓系白血病细胞凋亡并促进其分化。
Front Pharmacol. 2020 Aug 28;11:1321. doi: 10.3389/fphar.2020.01321. eCollection 2020.
6
Anticancer Attributes of Cantharidin: Involved Molecular Mechanisms and Pathways.斑蝥素的抗癌特性：涉及的分子机制和途径。
Molecules. 2020 Jul 19;25(14):3279. doi: 10.3390/molecules25143279.
7
The natural anticancer agent cantharidin alters GPI-anchored protein sorting by targeting Cdc1-mediated remodeling in endoplasmic reticulum.天然抗癌剂斑蝥素通过靶向 Cdc1 介导的内质网重塑来改变 GPI-锚定蛋白的分拣。
J Biol Chem. 2019 Mar 15;294(11):3837-3852. doi: 10.1074/jbc.RA118.003890. Epub 2019 Jan 18.
8
Recent Advances in Herbal Medicines for Digestive System Malignancies.用于消化系统恶性肿瘤的草药药物的最新进展
Front Pharmacol. 2018 Nov 20;9:1249. doi: 10.3389/fphar.2018.01249. eCollection 2018.
9
A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology.基于系统生物学的方法揭示中药青黛治疗慢性髓性白血病作用的分子机制，涉及网络药理学和分子对接技术的整合。
Med Sci Monit. 2018 Jun 23;24:4305-4316. doi: 10.12659/MSM.908104.
斑蝥素通过钙/蛋白激酶C调节的内质网应激途径诱导人膀胱癌细胞凋亡。
Am J Chin Med. 2015;43(3):581-600. doi: 10.1142/S0192415X15500366.
4
Cantharidin inhibits cell proliferation and promotes apoptosis in tongue squamous cell carcinoma through suppression of miR-214 and regulation of p53 and Bcl-2/Bax.斑蝥素通过抑制miR-214以及调节p53和Bcl-2/Bax来抑制舌鳞状细胞癌的细胞增殖并促进其凋亡。
Oncol Rep. 2015 Jun;33(6):3061-8. doi: 10.3892/or.2015.3942. Epub 2015 Apr 28.
5
Cantharidin induces DNA damage and inhibits DNA repair-associated protein expressions in TSGH8301 human bladder cancer cell.斑蝥素诱导TSGH8301人膀胱癌细胞的DNA损伤并抑制DNA修复相关蛋白表达。
Anticancer Res. 2015 Feb;35(2):795-804.
6
Chronic myeloid leukaemia.慢性髓性白血病。
Lancet. 2015 Apr 11;385(9976):1447-59. doi: 10.1016/S0140-6736(13)62120-0. Epub 2014 Dec 5.
7
Cantharidin induces G2/M phase arrest by inhibition of Cdc25c and Cyclin A and triggers apoptosis through reactive oxygen species and the mitochondria‑dependent pathways of A375.S2 human melanoma cells.斑蝥素通过抑制 Cdc25c 和细胞周期蛋白 A 诱导 G2/M 期阻滞，并通过活性氧和 A375.S2 人黑素瘤细胞中依赖线粒体的途径引发细胞凋亡。
Int J Oncol. 2014 Dec;45(6):2393-402. doi: 10.3892/ijo.2014.2689. Epub 2014 Sep 30.
8
Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr/Abl-dependent and -independent mechanisms.抗风湿药物金诺芬通过依赖和不依赖Bcr/Abl的机制诱导对伊马替尼耐药的慢性髓性白血病细胞凋亡。
Oncotarget. 2014 Oct 15;5(19):9118-32. doi: 10.18632/oncotarget.2361.
9
PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells through inhibition on the Wnt/β-catenin pathway by phosphorylation and degradation of β-catenin.蛋白磷酸酶2A（PP2A）抑制剂通过磷酸化和降解β-连环蛋白来抑制Wnt/β-连环蛋白信号通路，从而抑制胰腺癌细胞PANC-1的迁移和生长。
Oncol Rep. 2014 Aug;32(2):513-22. doi: 10.3892/or.2014.3266. Epub 2014 Jun 13.
10
Effect of cantharidins in chemotherapy for hepatoma: a retrospective cohort study.斑蝥素在肝癌化疗中的作用：一项回顾性队列研究。
Am J Chin Med. 2014;42(3):561-7. doi: 10.1142/S0192415X14500360.