...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma.
【24h】

Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma.

机译：STAT-3的抑制导致头颈部鳞状细胞癌中西妥昔单抗的敏感性更高。

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

OBJECTIVE: The inhibition of epidermal growth factor receptor (EGFr) with the monoclonal antibody cetuximab reduces cell proliferation and survival which correlates with increased DNA damage. Since the signal transducer and activator of transcription-3 (STAT-3) is involved in the EGFr-induced signaling pathway, we hypothesized that depletion of STAT-3 may augment cetuximab-induced processes in human head and neck cancer cells. MATERIALS AND METHODS: Human head and neck squamous carcinoma cells (UM-SCC-5) were transfected with short hairpin RNA (shRNA) against STAT-3 (STAT3-2.4 and 2.9 cells). A mutated form of this shRNA was transfected for a control (NEG4.17 cells). Radiosensitivity was assessed by a standard colony formation assay. Proliferation was assessed by daily cell counts following treatment and apoptosis was assessed by an annexin V-FITC assay. The alkaline comet assay was used to assess DNA damage. RESULTS: The STAT-3 knockdown cells (STAT3-2.4 and STAT3-2.9 cells) demonstrated enhanced radiosensitivity compared to control NEG4.17 cells, which correlated with increased apoptosis. Also, the STAT-3 knockdown cells demonstrated decreased proliferation with cetuximab treatments compared to control cells (NEG4.17). The increased cetuximab sensitivity of the STAT-3 knockdown cells correlated with increased apoptosis and DNA damage compared to control cells (NEG4.17). CONCLUSION: These studies revealed that the greater anti-proliferative effects and increased cytotoxicity of cetuximab in the STAT3-2.4 and STAT3-2.9 cells compared to control NEG4.17 cells, may be a result of STAT3-mediated effects on cellular apoptosis and DNA damage.
机译：目的：用西妥昔单抗单克隆抗体抑制表皮生长因子受体（EGFr）可减少细胞增殖和存活，这与DNA损伤增加有关。由于信号转导和转录激活因子3（STAT-3）参与了EGFr诱导的信号通路，因此我们假设STAT-3的耗竭可能会增强西妥昔单抗在人头颈部癌细胞中诱导的过程。材料与方法：用针对STAT-3（STAT3-2.4和2.9细胞）的短发夹RNA（shRNA）转染人的头颈部鳞状癌细胞（UM-SCC-5）。将此shRNA的突变形式转染至对照（NEG4.17细胞）。通过标准菌落形成测定法评估放射敏感性。通过治疗后每天的细胞计数评估增殖，并通过膜联蛋白V-FITC测定评估凋亡。碱性彗星试验用于评估DNA损伤。结果：与对照组NEG4.17细胞相比，STAT-3敲低细胞（STAT3-2.4和STAT3-2.9细胞）具有增强的放射敏感性，这与凋亡增加有关。同样，与对照细胞（NEG4.17）相比，使用西妥昔单抗治疗的STAT-3敲低细胞显示出增殖减少。与对照细胞相比，STAT-3敲低细胞西妥昔单抗敏感性的增加与凋亡和DNA损伤的增加有关（NEG4.17）。结论：这些研究表明，与对照NEG4.17细胞相比，STAT3-2.4和STAT3-2.9细胞中西妥昔单抗具有更大的抗增殖作用并增加了细胞毒性，这可能是STAT3介导的对细胞凋亡和DNA损伤的影响。

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