• 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

甘草香豆素通过靶向从头脂生成和 TOPK-生存素轴使肝癌细胞对 ABT-737 敏感。

Glycycoumarin Sensitizes Liver Cancer Cells to ABT-737 by Targeting De Novo Lipogenesis and TOPK-Survivin Axis.

机构信息

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.

College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China.

出版信息

Nutrients. 2018 Mar 15;10(3):353. doi: 10.3390/nu10030353.

DOI:10.3390/nu10030353
PMID:29543705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5872771/
Abstract

Glycycoumarin (GCM) is a representative of bioactive coumarin compounds isolated from licorice, an edible and medicinal plant widely used for treating various diseases including liver diseases. The purpose of the present study is to examine the possibility of GCM as a sensitizer to improve the efficacy of BH3 mimetic ABT-737 against liver cancer. Three liver cancer cell lines (HepG2, Huh-7 and SMMC-7721) were used to evaluate the in vitro combinatory effect of ABT-737/GCM. HepG2 xenograft model was employed to assess the in vivo efficacy of ABT-737/GCM combination. Results showed that GCM was able to significantly sensitize liver cancer cells to ABT-737 in both in vitro and in vivo models. The enhanced efficacy by the combination of ABT-737 and GCM was attributed to the inactivation of T-LAK cell-originated protein kinase (TOPK)-survivin axis and inhibition of de novo lipogenesis. Our findings have identified induction of TOPK-survivin axis as a novel mechanism rendering cancer cells resistant to ABT-737. In addition, ABT-737-induced platelet toxicity was attenuated by the combination. The findings of the present study implicate that bioactive coumarin compound GCM holds great potential to be used as a novel chemo-enhancer to improve the efficacy of BH3 mimetic-based therapy.

摘要

甘草香豆素（GCM）是从甘草中分离出的生物活性香豆素化合物的代表，甘草是一种广泛用于治疗各种疾病（包括肝病）的食用和药用植物。本研究的目的是研究 GCM 作为增敏剂的可能性，以提高 BH3 模拟物 ABT-737 对肝癌的疗效。使用三种肝癌细胞系（HepG2、Huh-7 和 SMMC-7721）评估 ABT-737/GCM 的体外联合效应。采用 HepG2 异种移植模型评估 ABT-737/GCM 联合的体内疗效。结果表明，GCM 能够在体外和体内模型中显著增敏肝癌细胞对 ABT-737 的敏感性。ABT-737 和 GCM 联合的增效作用归因于 T-LAK 细胞起源的蛋白激酶（TOPK）-survivin 轴的失活和从头脂生成的抑制。我们的研究结果表明，诱导 TOPK-survivin 轴是赋予癌细胞对 ABT-737 耐药的新机制。此外，ABT-737 诱导的血小板毒性通过联合作用得到减轻。本研究的结果表明，生物活性香豆素化合物 GCM 具有作为新型化疗增强剂的巨大潜力，可提高基于 BH3 模拟物的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/b6ae2d07a67a/nutrients-10-00353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/c6300ca90de5/nutrients-10-00353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/cc4fa26fdc02/nutrients-10-00353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/6dc84c137e71/nutrients-10-00353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/45770194acb0/nutrients-10-00353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/579fcf5e2a6e/nutrients-10-00353-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/5df2a7c6fa90/nutrients-10-00353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/b6ae2d07a67a/nutrients-10-00353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/c6300ca90de5/nutrients-10-00353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/cc4fa26fdc02/nutrients-10-00353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/6dc84c137e71/nutrients-10-00353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/45770194acb0/nutrients-10-00353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/579fcf5e2a6e/nutrients-10-00353-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/5df2a7c6fa90/nutrients-10-00353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ea8/5872771/b6ae2d07a67a/nutrients-10-00353-g007.jpg

相似文献

1
Glycycoumarin Sensitizes Liver Cancer Cells to ABT-737 by Targeting De Novo Lipogenesis and TOPK-Survivin Axis.甘草香豆素通过靶向从头脂生成和 TOPK-生存素轴使肝癌细胞对 ABT-737 敏感。
Nutrients. 2018 Mar 15;10(3):353. doi: 10.3390/nu10030353.
2
Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase.甘草香豆素通过直接靶向T淋巴细胞活化杀伤细胞源蛋白激酶发挥抗肝癌活性。
Oncotarget. 2016 Oct 4;7(40):65732-65743. doi: 10.18632/oncotarget.11610.
3
Bcl-xL inhibition by molecular-targeting drugs sensitizes human pancreatic cancer cells to TRAIL.分子靶向药物对Bcl-xL的抑制作用使人类胰腺癌细胞对TRAIL敏感。
Oncotarget. 2015 Dec 8;6(39):41902-15. doi: 10.18632/oncotarget.5881.
4
Norcantharidin combined with ABT-737 for hepatocellular carcinoma: Therapeutic effects and molecular mechanisms.去甲斑蝥素联合ABT-737治疗肝细胞癌：治疗效果与分子机制
World J Gastroenterol. 2016 Apr 21;22(15):3962-8. doi: 10.3748/wjg.v22.i15.3962.
5
Platinum compounds sensitize ovarian carcinoma cells to ABT-737 by modulation of the Mcl-1/Noxa axis.铂类化合物通过调节 Mcl-1/Noxa 轴使卵巢癌细胞对 ABT-737 敏感。
Apoptosis. 2013 Apr;18(4):492-508. doi: 10.1007/s10495-012-0799-x.
6
Increased efficacy of CDDP in a xenograft model of hepatoblastoma using the apoptosis sensitizer ABT-737.使用凋亡敏化剂 ABT-737 提高肝癌异种移植模型中 CDDP 的疗效。
Oncol Rep. 2013 Feb;29(2):646-52. doi: 10.3892/or.2012.2150. Epub 2012 Nov 27.
7
The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to carboplatin.Bcl-2/Bcl-XL家族抑制剂ABT-737使卵巢癌细胞对卡铂敏感。
Clin Cancer Res. 2007 Dec 1;13(23):7191-8. doi: 10.1158/1078-0432.CCR-07-0362.
8
HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2.HSP90 抑制剂（NVP-AUY922）增强了表达 BCL-2 的小细胞肺癌中 BCL-2 抑制剂（ABT-737）的抗癌作用。
Cancer Lett. 2017 Dec 28;411:19-26. doi: 10.1016/j.canlet.2017.09.040. Epub 2017 Oct 4.
9
ABT-737 Synergizes with Cisplatin Bypassing Aberration of Apoptotic Pathway in Non-small Cell Lung Cancer.ABT-737与顺铂协同作用，绕过非小细胞肺癌凋亡途径的异常。
Neoplasia. 2017 Apr;19(4):354-363. doi: 10.1016/j.neo.2017.02.008. Epub 2017 Mar 17.
10
The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma.BH3 模拟物 ABT-737 提高紫杉醇治疗肝癌的疗效。
BMC Cancer. 2011 Aug 19;11:362. doi: 10.1186/1471-2407-11-362.

引用本文的文献

1
Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.植物化学物质通过调节 AMPK/PGC-1α 信号通路来调节癌症代谢。
BMC Cancer. 2024 Sep 2;24(1):1079. doi: 10.1186/s12885-024-12715-7.
2
The Potential of Glycyrrhiza from "Medicine Food Homology" in the Fight against Digestive System Tumors.“药食同源”甘草在消化系统肿瘤防治中的潜力。
Molecules. 2023 Nov 22;28(23):7719. doi: 10.3390/molecules28237719.
3
Absorption, tissue distribution, and excretion of glycycoumarin, a major bioactive coumarin from Chinese licorice ( Fisch).

本文引用的文献

1
Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.山奈酚增加人急性早幼粒细胞白血病细胞凋亡并抑制多药耐药基因。
J Cell Biochem. 2018 Feb;119(2):2288-2297. doi: 10.1002/jcb.26391. Epub 2017 Oct 20.
2
Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity.在谷氨酸兴奋性毒性中，Bcl-xL 的抑制可防止 ΔN-Bcl-xL 在线粒体内膜上的促死亡作用。
Cell Death Differ. 2017 Nov;24(11):1963-1974. doi: 10.1038/cdd.2017.123. Epub 2017 Aug 4.
3
Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy.
甘草香豆素（一种源自中国甘草（ Fisch）的主要生物活性香豆素）的吸收、组织分布及排泄情况
Front Pharmacol. 2023 Jul 7;14:1216985. doi: 10.3389/fphar.2023.1216985. eCollection 2023.
4
Targeted Inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer.靶向抑制脂蛋白脂肪酶/脂肪酸结合蛋白4/肉碱棕榈酰转移酶1脂肪酸代谢轴可有效预防非酒精性脂肪性肝炎进展为肝癌。
Int J Biol Sci. 2021 Oct 11;17(15):4207-4222. doi: 10.7150/ijbs.64714. eCollection 2021.
5
Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma.鳖甲煎丸通过Akt/GSK-3β/Snail信号通路抑制肝细胞癌的发生和转移。
Front Pharmacol. 2021 Mar 8;12:610158. doi: 10.3389/fphar.2021.610158. eCollection 2021.
针对抗凋亡 BCL-2 家族的差异化成瘾进行癌症治疗。
Nat Commun. 2017 Jul 17;8:16078. doi: 10.1038/ncomms16078.
4
CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.CK2和PI3K是槲皮素在慢性淋巴细胞白血病中的直接分子靶点。
Oncotarget. 2017 Jun 27;8(26):42571-42587. doi: 10.18632/oncotarget.17246.
5
Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival.抑制肝内脂质生成通过增加抗氧化防御和促进细胞存活来增强肝肿瘤发生。
Nat Commun. 2017 Mar 14;8:14689. doi: 10.1038/ncomms14689.
6
From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors.从基础的细胞凋亡发现到先进的选择性 BCL-2 家族抑制剂。
Nat Rev Drug Discov. 2017 Apr;16(4):273-284. doi: 10.1038/nrd.2016.253. Epub 2017 Feb 17.
7
Bone marrow microenvironment-derived signals induce Mcl-1 dependence in multiple myeloma.骨髓微环境衍生信号诱导多发性骨髓瘤对Mcl-1的依赖性。
Blood. 2017 Apr 6;129(14):1969-1979. doi: 10.1182/blood-2016-10-745059. Epub 2017 Feb 1.
8
YM155 enhances ABT-737-mediated apoptosis through Mcl-1 downregulation in Mcl-1-overexpressed cancer cells.YM155通过下调Mcl-1过表达癌细胞中的Mcl-1来增强ABT-737介导的细胞凋亡。
Mol Cell Biochem. 2017 May;429(1-2):91-102. doi: 10.1007/s11010-016-2938-0. Epub 2017 Jan 24.
9
Mcl-1 expression and JNK activation induces a threshold for apoptosis in Bcl-xL-overexpressing hematopoietic cells.Mcl-1表达和JNK激活诱导了过表达Bcl-xL的造血细胞凋亡的阈值。
Oncotarget. 2017 Feb 14;8(7):11042-11052. doi: 10.18632/oncotarget.14223.
10
Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway.甘草香豆素通过激活自噬和抑制内质网应激/GSK-3 介导的线粒体途径抑制肝细胞脂肪凋亡。
Sci Rep. 2016 Nov 30;6:38138. doi: 10.1038/srep38138.