• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Oncology Reports >Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN
【2h】

Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN

机译：通过激活PTEN与HDAC6抑制剂和COX-2抑制剂联合治疗的协同抗肿瘤作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Chemotherapy is one of the most effective non-surgical treatments for various types of tumor. Identifying different combinations of antitumor agents that can produce synergistic antitumor effects remains an important clinical strategy. In the present study, we showed that the combination of histone deacetylase 6 (HDAC6) inhibitor tubastatin A together with cyclooxygenase-2 (COX-2) inhibitor celecoxib resulted in synergistic antitumor effects in CAL 27 and SACC-83 cells. Treatment with celecoxib alone promoted the membrane translocation of phosphatase and tensin homolog (PTEN), indicating PTEN activation, and consequently led to protein kinase B (AKT) dephosphorylation (inactivation). Similarly, treatment with an HDAC6 inhibitor alone promoted PTEN membrane translocation and correspondingly dephosphorylated AKT. The combination of celecoxib and an HDAC6 inhibitor synergistically increased PTEN membrane translocation and inactivated AKT. Moreover, celecoxib enhanced the HDAC6 inhibitor-induced antitumor effects in PTEN-deficient U-87 MG cells that had been stably transfected with wild-type PTEN, but not in the same cell line stably transfected with mutant PTEN-K163R, which cannot be activated by HDAC6 inhibitors. In summary, the results indicated that the COX-2 inhibitor celecoxib enhanced the HDAC6 inhibitor-induced antitumor effects by activating the PTEN/AKT signaling pathway.
机译：化学疗法是治疗各种类型肿瘤最有效的非手术疗法之一。鉴定可以产生协同抗肿瘤作用的抗肿瘤药的不同组合仍然是重要的临床策略。在本研究中，我们表明组蛋白脱乙酰基酶6（HDAC6）抑制剂tubastatin A与环氧合酶2（COX-2）抑制剂塞来昔布的组合在CAL 27和SACC-83细胞中产生协同抗肿瘤作用。单独使用塞来昔布治疗可促进磷酸酶和张力蛋白同源物（PTEN）的膜移位，表明PTEN激活，并因此导致蛋白激酶B（AKT）脱磷酸作用（失活）。类似地，单独使用HDAC6抑制剂治疗可促进PTEN膜易位并相应地使AKT去磷酸化。塞来昔布和HDAC6抑制剂的组合协同增加PTEN膜移位和AKT失活。此外，塞来昔布在已被野生型PTEN稳定转染的PTEN缺陷型U-87 MG细胞中增强了HDAC6抑制剂诱导的抗肿瘤作用，但在无法被突变PTEN-K163R稳定转染的同一细胞系中却未增强通过HDAC6抑制剂。总之，结果表明，COX-2抑制剂塞来昔布通过激活PTEN / AKT信号通路增强了HDAC6抑制剂诱导的抗肿瘤作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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