• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell Biology and Toxicology >The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy
【24h】

The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy

机译：Caspase-1 / GSDMD介导的猪毒素诱导的细胞死亡中的作用和自噬鼻咽癌中鼻咽癌的毒性表型

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that pyroptosis is associated with the development of cancer; however, the function and mechanism of pyroptosis in NPC remain obscure. In this study, we observed that Taxol treatment caused pyroptotic cell death, along with activation of Caspase-1 and maturation of IL-1 beta, as well as cleavage of GSDMD, which is the canonical pyroptosis executor. Furthermore, Taxol-induced pyroptotic cell death could be suppressed by Caspase-1 inhibitor (Z-YVAD-FMK) and GSDMD knockout. Moreover, NPC parental cells demonstrated higher levels of pyroptosis than Taxol-resistant cells, and pyroptosis mediated by Caspase-1/GSDMD suppression induced by a Caspase-1 inhibitor and GSDMD knockout could induce a Taxol-resistant phenotype in vitro and in vivo. By transfecting an siRNA targeting Beclin-1 into NPC Taxol-resistant cells, we discovered that autophagy could negatively regulate pyroptosis by inhibiting Caspase-1/GSDMD activation. Taken together, our results indicated that Caspase-1/GSDMD mediated Taxol-induced pyroptosis and a Taxol-resistant phenotype in NPC cell lines, which may be regulated by autophagy. Thus, we provide novel insight into the mechanisms of Taxol-induced cell death and a promising approach to improve the therapeutic outcomes of patients with advanced NPC.
机译：紫杉醇已被广泛用作治疗晚期鼻咽癌（NPC）的一线化学治疗剂。然而，获得的耐药性导致临床治疗困难。嘟素凋亡是一种新发现的编程细胞死亡途径，Caspase-1和汽笛D（GSDMD）在驾驶规范糊状症方面发挥关键作用。越来越多的证据表明糊化酶与癌症的发展有关;然而，NPC糊化酶的功能和机制仍然模糊不清。在这项研究中，我们观察到紫杉醇治疗导致糊化细胞死亡，以及激活Caspase-1和IL-1β的成熟，以及GSDMD的切割，即典型糊化酶执行器。此外，Caspase-1抑制剂（Z-YVAD-FMK）和GSDMD敲除可以抑制紫杉醇诱导的糊状细胞死亡。此外，NPC亲本细胞表现出比紫杉醇抗性细胞的糊酶水平较高，并且通过Caspase-1抑制剂和GSDMD敲除诱导的Caspase-1 / GSDMD抑制诱导的糊状酶可以在体外和体内诱导紫杉醇抗性表型。通过将靶向Beclin-1的siRNA转染到NPC紫杉醇抗性细胞中，我们发现通过抑制Caspase-1 / GSDMD活化来对γ-1 / GSDMD活化产生抗凋亡。我们的结果表明，Caspase-1 / GSDMD介导的紫杉醇诱导的毒催化剂和NPC细胞系中的紫杉醇抗性表型，其可以通过自噬调节。因此，我们提供了对紫杉醇诱导的细胞死亡机制的新颖洞察力以及提高高级NPC患者治疗结果的有希望的方法。

著录项

  • 来源
    《Cell Biology and Toxicology》 |2020年第5期|共21页
  • 作者

    Wang Xianyao; Li Heqing; Li Wei; Xie Jun; Wang Fengjun; Peng Xiaowei; Song Yexun; Tan Guolin;

  • 作者单位

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp 3 Changsha Hunan Peoples R China;

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp 3 Changsha Hunan Peoples R China;

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp 3 Changsha Hunan Peoples R China;

    Hunan Childrens Hosp Dept Otolaryngol Head &

    Neck Surg Changsha 410013 Hunan Peoples R China;

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp Changsha 410013 Hunan Peoples R China;

    Hunan Prov Canc Hosp Dept Oncol Plast Surg Changsha 410007 Hunan Peoples R China;

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp 3 Changsha Hunan Peoples R China;

    Cent South Univ Dept Otolaryngol Head &

    Neck Surg Xiangya Hosp 3 Changsha Hunan Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 Q28;
  • 关键词

    Nasopharyngeal carcinoma; Pyroptosis; Caspase-1; GSDMD; Taxol resistance;

    机译：鼻咽癌;腐蛋白;Caspase-1;GSDMD;紫杉醇抗性;

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