基本信息来源于合作网站,原文需代理用户跳转至来源网站获取       
摘要:
Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR),contributing to aggressive metastatic disease.Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me),a glycyrrhetinic acid derivative,reportedly improves the therapeutic response to erlotinib (ERL),an EGFR tyrosine kinase inhibitor.In the present study,we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R(ERL-resistant) cells to ERL.Herein,we first established the selectivity of ERL-induced drug resistance in the HCC827R cells,which was sensitized when ERL was combined with CDODA-Me (2 μ.M),shifting the IC5o from 23.48 μM to 5.46 μM.Subsequently,whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44% of the whole transcriptome (WT)) and 174 upregulated genes (0.36% of the WT),of which approximately 80%were unique to the ERL + CDODA-Me group.Synergistic effects centered on losses to cell cycle pro-gression transcripts,a reduction of minichromosome maintenance complex components (MCM2-7),all key components of the Cdc45·MCM2-7GINS (CMG) complex,and replicative helicases;these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress,including sulfiredoxin 1,heme oxygenase 1,and stress-induced growth inhibitor 1.Collectively,these findings indicate that the synergistic therapeutic effects of ERL +CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.
内容分析
关键词云
关键词热度
相关文献总数  
(/次)
(/年)
文献信息
篇名 Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells
来源期刊 药物分析学报(英文版) 学科
关键词
年,卷(期) 2021,(6) 所属期刊栏目 Original Articles
研究方向 页码范围 799-807
页数 9页 分类号
字数 语种 英文
DOI
五维指标
传播情况
(/次)
(/年)
引文网络
引文网络
二级参考文献  (0)
共引文献  (0)
参考文献  (0)
节点文献
引证文献  (0)
同被引文献  (0)
二级引证文献  (0)
2021(0)
  • 参考文献(0)
  • 二级参考文献(0)
  • 引证文献(0)
  • 二级引证文献(0)
引文网络交叉学科
相关学者/机构
期刊影响力
药物分析学报(英文)
双月刊
2095-1779
61-1484/R
大16开
西安市雁塔西路76号
1985
eng
出版文献量(篇)
639
总下载数(次)
0
论文1v1指导