...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Korean medical science >Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.
【24h】

Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.

机译：Bcl-xL的组合可增强白藜芦醇和氯法拉滨在恶性间皮瘤H-2452细胞中的生长抑制和凋亡诱导作用。

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

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
机译：Bcl-2家族的关键抗凋亡蛋白Mcl-1和Bcl-xL作为细胞存活和耐药性中的重要分子而受到关注。在这项研究中，我们调查了Bcl-xL的抑制作用是否会影响人恶性间皮瘤H-2452细胞中白藜芦醇和氯法拉滨的同时治疗，从而影响细胞生长和凋亡。白藜芦醇和氯法拉滨降低Mcl-1蛋白水平，但对Bcl-xL水平影响不大。在存在两种化合物的情况下，在RT-PCR分析中未观察到Mcl-1 mRNA水平的任何可检测到的变化，而用蛋白酶体抑制剂MG132预处理导致其积累至远高于基础水平的水平。 Bcl-xL的敲低抑制了细胞增殖，在DNA流式细胞术检测中出现了G2 / M期的细胞蓄积，并且出现了sub-G0 / G1峰。细胞生长的抑制伴随着caspase-3 / 7活性的增加以及procaspase-3及其底物多聚（ADP-核糖）聚合酶的裂解，以及膜联蛋白V结合试验中细胞凋亡率的增加。总体而言，我们的数据表明，Bcl-xL降低策略大大增强了白藜芦醇和氯法拉滨诱导凋亡的功效，其中同时靶向Mcl-1和Bcl-xL可能是治疗恶性间皮瘤的更有效策略。

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