...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>British Journal of Cancer >Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment
【24h】

Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment

机译：重新扫描筛网鉴定Mebendazole作为临床候选者，以协同与多西紫杉醇进行前列腺癌治疗的临床候选者

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle chemoresistant prostate cancer by enhancing the efficacy of docetaxel. Methods We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs ( n ?=?857) from repurposing libraries, with cytotoxicity quantified using High Content Imaging Analysis. Results Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment, no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival. Conclusions Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants further clinical evaluation.
机译：前列腺癌中的Cocetaxel化疗对生存产生了适度的影响。迄今为止，开发组合疗法的努力尚未翻译成新的治疗方法。我们试图通过提高多西紫杉醇的疗效来制定一种新的治疗策略来解决化学诱导的前列腺癌。方法我们通过使用临床相关基因型驱动的小鼠衍生的前列腺癌细胞系进行了药物修复筛网。单独用多西紫杉醇处理细胞，或者与重新扫描文库中的药物（N？=β857）组合，具有使用高含量成像分析的细胞毒性。结果选择兆甲唑（抑制微管组件的一个抑制微管组件的药物）作为铅药物，并显示出在体外和体内杀死多西紫杉醇介导的细胞杀死。微管结构的双重靶向与增加的G2 / M有丝分裂块和增强的细胞死亡有关。令人惊讶的是，在联合多西紫杉醇和兆唑治疗之后，没有正确分开细胞，形成导致动脉倍增子细胞的多极锭子。孕妇诱捕多西紫杉醇和梅白唑抑制体内前列腺肿瘤生长和无进展的存活率。结论Docetaxel和Mebendazole的微管动力学的独特方面，导致细胞凋亡增加和肿瘤生长减少。我们的数据支持新的梅白唑/多西紫杉醇治疗的新概念，可根据临床评估。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号