吐温 20 通过与 MDR 蛋白上的药物结合区和 ATP 结合区相互作用,逆转 ABC 转运体介导的多药耐药性癌症和耐药性抑郁症的潜能。

IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng
{"title":"吐温 20 通过与 MDR 蛋白上的药物结合区和 ATP 结合区相互作用,逆转 ABC 转运体介导的多药耐药性癌症和耐药性抑郁症的潜能。","authors":"Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng","doi":"10.1080/1061186X.2024.2429006","DOIUrl":null,"url":null,"abstract":"<p><p>Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters <i>in vitro</i> and to evaluate its potential for overcoming drug resistance in two models: an <i>in vitro</i> cancer MDR model and an <i>in vivo</i> TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the <i>in vivo</i> depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both <i>in vitro</i> and <i>in vivo</i>, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.3000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins.\",\"authors\":\"Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng\",\"doi\":\"10.1080/1061186X.2024.2429006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters <i>in vitro</i> and to evaluate its potential for overcoming drug resistance in two models: an <i>in vitro</i> cancer MDR model and an <i>in vivo</i> TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the <i>in vivo</i> depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both <i>in vitro</i> and <i>in vivo</i>, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.</p>\",\"PeriodicalId\":15573,\"journal\":{\"name\":\"Journal of Drug Targeting\",\"volume\":\" \",\"pages\":\"1-14\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Targeting\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1061186X.2024.2429006\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Targeting","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1061186X.2024.2429006","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

药物外排转运体,尤其是那些属于 ATP 结合盒(ABC)转运体超家族的转运体,在各种耐药性问题中发挥着至关重要的作用,包括癌症中的多药耐药性(MDR)和重度抑郁症患者的耐药性抑郁症(TRD)。其中的关键转运体包括P-糖蛋白(P-gp)、多药耐药蛋白1(MRP1)和乳腺癌耐药蛋白(BCRP)。本研究旨在探讨聚氧乙烯(20)山梨糖醇酐单月桂酸酯(吐温 20)在体外对这些外流转运体的调节作用,并评估其在两种模型(体外癌症 MDR 模型和体内 TRD 模型)中克服耐药性的潜力。研究结果表明,0.001% 的吐温 20 能明显抑制所有三种转运体的外流作用。此外,0.005% 吐温 20 还能有效逆转各种癌症 MDR 细胞系对紫杉醇、长春新碱、多柔比星和米托蒽醌的耐药性。在体内抑郁样行为模型中,0.01% 吐温 20 明显增强了氟西汀的抗抑郁和抗焦虑作用。鉴于吐温 20 对 P-gp、MRP1 和 BCRP 有很强的抑制作用,而且在体外和体内都能逆转耐药性,因此它是解决转运体介导的耐药性问题的理想候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins.

Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters in vitro and to evaluate its potential for overcoming drug resistance in two models: an in vitro cancer MDR model and an in vivo TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the in vivo depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both in vitro and in vivo, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信