CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
PBK/TOPK 抑制剂 OTS964 耐药由 ABCB1 依赖性转运功能介导：体外和体内研究
英文原题：PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study.
查看英文原题
PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study.
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中文摘要
ABCB1过表达显著降低了药物筛选细胞和基因转染细胞（两者均过表达ABCB1）对OTS964的敏感性，且这种耐药性可被维拉帕米（一种已知的ABCB1抑制剂）拮抗。在荷瘤小鼠中也一致观察到类似趋势。OTS964可刺激ABCB1的ATP酶活性并上调ABCB1的表达水平，从而导致对其他ABCB1底物药物（如紫杉醇）产生诱导性耐药。OTS964获得了相当的亲和力评分，并能对接至人ABCB1蛋白的底物结合位点。补充信息：在线版本包含补充材料，可访问10.1186/s12943-022-01512-0获取。
展开英文摘要原文
UNLABELLED: ABCB1 overexpression significantly desensitized both drug-selected and gene-transfected cells, which overexpress ABCB1, to OTS964 and that this drug resistance can be antagonized by verapamil, a known ABCB1 inhibitor. Consistently, a similar trend was observed in tumor-bearing mice.
OTS964 stimulated ATPase activity of ABCB1 and upregulated expression levels of ABCB1, resulting in induced resistance to other ABCB1 substrate-drugs, such as paclitaxel. OTS964 received a comparable affinity score and can dock into the substrate-binding site of human ABCB1 protein. . SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10. 1186/s12943-022-01512-0.
论文信息
- 作者
- Yang Y、Teng QX、Wu ZX、Wang JQ、Lei ZN、Lusvarghi S、Ambudkar SV、Ji N
- 第一作者单位
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York City, NY, 11439, USA.United States
- 通讯作者单位
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York City, NY, 11439, USA. chenz@stjohns.edu.United States
- 文献类型
- 读者来信 · 美国 NIH 院内研究 · 非美国政府资助研究
- 期刊
- Molecular cancer2022 Feb 8
- 原文标识
- PubMed 35135547 · DOI 10.1186/s12943-022-01512-0
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