首页    期刊浏览 2024年12月13日 星期五
登录注册

文章基本信息

  • 标题:Homoharringtonine induces apoptosis and inhibits STAT3 via IL-6/JAK1/STAT3 signal pathway in Gefitinib-resistant lung cancer cells
  • 本地全文:下载
  • 作者:Wei Cao ; Ying Liu ; Ran Zhang
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2015
  • 卷号:5
  • 期号:1
  • DOI:10.1038/srep08477
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia , on Gefitinib-resistant NSCLC cell lines in vitro and in viv o. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGFβ signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo . Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
国家哲学社会科学文献中心版权所有