• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >The mechanism and kinetics of reovirus T1- and T3-induced apoptosis of human colon and pancreatic cancer cells.
【24h】

The mechanism and kinetics of reovirus T1- and T3-induced apoptosis of human colon and pancreatic cancer cells.

机译：呼肠孤病毒T1和T3诱导人结肠癌和胰腺癌细胞凋亡的机制和动力学。

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

Reovirus is an "oncolytic" virus which kills cancer cells, but not normal cells. Reovirus also induces apoptosis in vivo and in vitro with T3 strains inducing apoptosis to a greater extent than T1 strains. The hypothesis of this study was that T1 and T3 reovirus strains would induce apoptosis in HT-29 colon and Panc-1 pancreatic cancer cell lines. The specific aims of this project were to determine: (1) if T1L, T3D, and T3A kill HT-29 and Panc-1 cells by apoptosis, (2) whether the kinetics (rate and magnitude) of reovirus-induced cell death vary with viral dose and (3) death signaling pathways activated in infected cells. Strains T1L, T3A, and T3D killed HT-29 and Panc-1 cancer cells primarily by apoptosis at all MOIs tested and resulted in activation of both mitochondrial and death receptor apoptotic pathways in Panc-1 and HT-29 cells. Downregulation of TRAIL protein expression was observed in HT-29 cells after infection with T1 and T3 strains, but remained constant in infected Panc-1 cells. Upregulation of TRAIL-receptor 1 (DR4) protein expression was detected in T3-infected HT-29 and Panc-1, but not in T1-infected cells. Strain-specific differences in the kinetics of apoptosis, in which T3D-induced less apoptosis than T1L and T3A, were observed at MOI 50 in both HT-29 and Panc-1 cells, and correlated with the ability of virus to productively infect the majority of cells in culture. Increasing the MOI from 50 to 500 or 5000 substantially increased the kinetics of apoptosis in HT-29 cells, and to a lesser extent in Panc-1 cells, and eliminated strain-specific differences in the kinetics of cell death observed at MOI 50. These results show for the first time that reovirus T1L can effectively induce apoptosis of infected cells and that T1- and T3-induced apoptosis is mediated via the same major apoptotic pathways. Strain-specific differences in the kinetics of viral-induced apoptosis at different MOIs and in TRAIL and DR4 expression in two different cancer cell types, suggest that both T1 and T3 reovirus strains should be tested for use as cancer therapeutics and optimized with respect to strain and dose for specific cancer cell types.
机译：呼肠孤病毒是一种“溶瘤”病毒，可以杀死癌细胞，但不能杀死正常细胞。呼肠孤病毒还与T1株相比，在体内和体外诱导T3株诱导细胞凋亡。该研究的假设是，T1和T3呼肠孤病毒株将诱导HT-29结肠和Panc-1胰腺癌细胞系凋亡。该项目的具体目标是确定：（1）T1L，T3D和T3A是否通过凋亡杀死HT-29和Panc-1细胞；（2）呼肠孤病毒诱导的细胞死亡的动力学（速率和幅度）是否发生变化病毒剂量和（3）在感染细胞中激活的死亡信号通路。菌株T1L，T3A和T3D主要​​通过所有测试的MOI的凋亡来杀死HT-29和Panc-1癌细胞，并导致Panc-1和HT-29细胞中的线粒体和死亡受体凋亡途径均被激活。 T1和T3株感染后，在HT-29细胞中观察到TRAIL蛋白表达的下调，但在受感染的Panc-1细胞中保持恒定。在感染T3的HT-29和Panc-1中检测到TRAIL受体1（DR4）蛋白表达的上调，但在感染T1的细胞中未检测到。在HT-29和Panc-1细胞中，在MOI 50均观察到了细胞凋亡动力学的菌株特异性差异，其中T3D诱导的细胞凋亡少于T1L和T3A，并且与病毒有效感染大多数细胞的能力有关。细胞的培养。将MOI从50增加到500或5000实质上增加了HT-29细胞凋亡的动力学，在Panc-1细胞中的程度也较小，并且消除了在MOI 50观察到的细胞死亡动力学中的菌株特异性差异。结果首次表明，呼肠孤病毒T1L可以有效诱导感染细胞的凋亡，而T1和T3诱导的凋亡是通过相同的主要凋亡途径介导的。在两种不同癌细胞类型中，病毒诱导的凋亡动力学在不同的MOI以及TRAIL和DR4表达中的菌株特异性差异，建议应同时测试T1和T3呼肠孤病毒菌株作为癌症治疗剂并针对其进行优化和特定癌细胞类型的剂量。

著录项

  • 作者

    Maxwell, Jill A.;

  • 作者单位

    East Carolina University.;

  • 授予单位 East Carolina University.;
  • 学科 Biology Microbiology.; Biology Cell.; Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 225 p.
  • 总页数 225
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;细胞生物学;肿瘤学;
  • 关键词

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