• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Complementary and Alternative Medicine >Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology
【24h】

Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology

机译：通过网络药理学研究中药扶正抗癌对EGFR突变阳性肺腺癌的作用机制

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

摘要

Chinese traditional herbal medicine Fuzhengkangai (FZKA) formulation combination with gefitinib can overcome drug resistance and improve the prognosis of lung adenocarcinoma patients. However, the pharmacological and molecular mechanisms underlying the active ingredients, potential targets, and overcome drug resistance of the drug are still unclear. Therefore, it is necessary to explore the molecular mechanism of FZKA. A systems pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of EGFR-TKI resistance with clinically effective herb formula. The differential gene expressions between EGFR-TKI sensitive and resistance cell lines were calculated and used to find overlap from targets as core targets. The prognosis of core targets was validated from the cancer genome atlas (TCGA) database by Cox regression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment is applied to analysis core targets for revealing mechanism in biology. The results showed that 35 active compounds of FZKA can interact with eight core targets proteins (ADRB2, BCL2, CDKN1A, HTR2C, KCNMA1, PLA2G4A, PRKCA and LYZ). The risk score of them were associated with overall survival and relapse free time (HR?=?6.604, 95% CI: 2.314–18.850; HR?=?5.132, 95% CI: 1.531–17.220). The pathway enrichment suggested that they involved in EGFR-TKI resistance and non-small cell lung cancer pathways, which directly affect EGFR-TKI resistance. The molecular docking showed that licochalcone a and beta-sitosterol can closely bind two targets (BCL2 and PRKCA) that involved in EGFR-TKI resistance pathway. This study provided a workflow for understanding mechanism of CHM for against drug resistance.
机译：中草药扶正康艾（FZKA）制剂与吉非替尼联合使用可克服耐药性并改善肺腺癌患者的预后。但是，尚不清楚活性成分，潜在靶点和克服药物耐药性的药理和分子机理。因此，有必要探索FZKA的分子机制。采用基于系统药理学和生物信息学的方法来研究具有临床有效草药配方的EGFR-TKI抗药性的分子发病机理。计算EGFR-TKI敏感和耐药细胞系之间的差异基因表达，并将其用于发现靶标作为核心靶标的重叠。通过Cox回归从癌症基因组图谱（TCGA）数据库中验证了核心目标的预后。京都基因与基因组百科全书（KEGG）途径富集被用于分析核心靶标以揭示生物学机制。结果表明，FZKA的35种活性化合物可以与8种核心靶蛋白（ADRB2，BCL2，CDKN1A，HTR2C，KCNMA1，PLA2G4A，PRKCA和LYZ）相互作用。他们的风险评分与总生存期和无复发时间相关（HR≥6.204，95％CI：2.314-18.850; HR≥5.132，95％CI：1.531.17.220）。该途径的丰富性提示它们参与了EGFR-TKI耐药性和非小细胞肺癌通路，它们直接影响了EGFR-TKI耐药性。分子对接表明，里考康宁a和β-谷固醇可以紧密结合与EGFR-TKI耐药途径有关的两个靶标（BCL2和PRKCA）。这项研究提供了一个工作流程，用于了解CHM抗药性的机制。

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