检验医学与临床2017，Vol.14Issue(2)：177-179,3.DOI:10.3969/j.issn.1672-9455.2017.02.010
以Ref-1为靶点的基因治疗在大肠癌5-FU化疗增敏中的作用及机制研究
Adenoviral vector mediated Ref-1 siRNA enhances the sensitivity of human colon cancer cells to 5-fluorouracil
摘要
Abstract
Objective To investigate the role of Ref‐1 as a target gene therapy in the treatment of colorectal cancer with 5‐FU and its possible mechanism .Methods We constructed chimeric adenoviral vector Ad5/F35 carrying human Ref‐1 siRNA (siRef‐1) to knockdown the expression of Ref‐1 in LOVO cells .Cellular proliferation was detected with MTT assay .Cell apoptosis was de‐tected by TUNEL .The expression of human Ref‐1 protein was determined by Western blotting analysis .NF‐κB DNA binding was determined by EMSA .Results SiRef‐1 enhanced sensitivity of LOVO cells to 5‐FU .The 50% inhibitory concentration (IC50) val‐ue for LOVO cells pretreatmented with SiRef‐1 and SiCon at 72 h after 5‐FU treatment was 1 .69μmol/L and 7 .04μmol/L ,respec‐tively .SiRef‐1 also increased 5‐FU‐induced cell apoptosis .The expression of Ref‐1 protein in LOVO cells was induced by 5‐FU in a dose dependent manner ,accompanied with the enhanced activity of NF‐κB ,and SiRef‐1 could effectively inhibit 5‐FU induced Ref‐1 expression and NF‐κB activation .Conclusion The treatment with Ref‐1 as the target can significantly enhance the sensitivity of 5‐FU in colorectal cancer cells ,and its mechanism may be mainly through the inhibition of NF‐κB in colorectal cancer cells .关键词
大肠癌/氧化还原因子-1/氟尿嘧啶/腺病毒载体/小干扰RNAKey words
colorectal cancer/Ref-1/fluorouracil/adenovirus vector/small interfering RNA引用本文复制引用
向德兵,董蕻,全晋,孙贵银,李梦侠,王东..以Ref-1为靶点的基因治疗在大肠癌5-FU化疗增敏中的作用及机制研究[J].检验医学与临床,2017,14(2):177-179,3.基金项目
国家自然科学基金资助项目（30972874）；重庆市卫生局科研项目（2011-2-445、2011-2-447、2012-1-106、2012-2-381）。 （）
