siRNA阻断NF-κB信号通路对食管鳞癌细胞增殖、耐药的影响

被引:8
作者
田芳 [1 ]
田卫红 [2 ]
许培荣 [3 ]
刘红涛 [3 ]
薛乐勋 [3 ]
机构
[1] 郑州大学基础医学院病理生理学教研室
[2] 安阳市肿瘤医院妇瘤科
[3] 郑州大学细胞生物学研究室
关键词
食管肿瘤; NF-kappaB; RNA干扰; siRNA;
D O I
10.13705/j.issn.1671-6825.2007.01.016
中图分类号
R735.1 [食管肿瘤];
学科分类号
100214 ;
摘要
目的:通过RNA干扰(RNAi)阻断食管鳞癌细胞中NF-κB信号通路,研究其与肿瘤细胞增殖、耐药的关系。方法:使用NF-κB p65 siRNA分别转染人食管鳞癌Eca109和EC9706细胞72h,以未转染的Eca109和EC9706细胞为对照,采用Western blot检测p65蛋白的表达;MTT法检测转染NF-κBp65siRNA24h、48h、72h后Eca109和EC9706细胞的增殖情况及转染同时联合应用不同质量浓度5-Fu(0mg/L,16.35mg/L,32.7mg/L,327mg/L,3270mg/L,6540mg/L)对Eca109和EC9706细胞增殖的影响。结果:①NF-κB亚单位p65在Eca109和EC9706细胞质中高表达,p65siRNA可有效阻断p65蛋白表达。②MTT实验表明,转染组细胞存活率较未转染组明显下降(P<0.05);与化疗药5-Fu联用,转染组和未转染组细胞的增殖活性随着5-Fu浓度的增加有下降趋势,但在同一浓度,转染p65siRNA的细胞与未转染组相比,细胞增殖活性明显下降(P<0.05)。结论:应用RNAi技术可有效干扰p65的表达,抑制食管鳞癌细胞的增殖,增强对化疗药5-Fu的敏感性。因此,可将阻断NF-κB信号通路作为基因治疗的靶点。
引用
收藏
页码:41 / 44
页数:4
相关论文
共 11 条
[1]  
Estimates of the worldwide mortality from25cancers in1990. Pisani P,Parkin DM,Bray F,et al. International Journal of Cancer . 1999
[2]  
The role of NF-κB in hepa-tocellular carcinoma cell. Wang JH,Huang QK,Chen MX. Chinese Medical Journal . 2003
[3]  
Constitutive nuclear factor-kappa B mRNA,protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumor cells. Wang W,Cassidy J. British Journal of Cancer . 2003
[4]  
The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer. Greten FR,Karin M. Cancer Letters . 2004
[5]  
NF-κB is constitutively activated in high-grade squamous intraepithe-lial lesions and squamous cell carcinomas of the human u-terine cervix. Nair A,Venkatraman M,Maliekal TT,et al. Oncegene . 2003
[6]  
Death and NF-kappaB in Tcell activation:life at the edge. Green DR. Molecular Cell . 2003
[7]  
Inhibition of constitutive NF-κB activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. Pham LV,Tamyo AT,Yoshimura LC,et al. J Immunol . 2003
[8]  
RNA interference. Hannon GJ. Nature . 2002
[9]  
Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear fac-ter-B signaling. Aggarwal S,Takada Y,Singh S,et al. International Journal of Cancer . 2004
[10]  
Oncology[P]. 英国专利:GB9814580D0,1998-09-02