| ODC, AdoMetDC双反义腺病毒对肺癌增殖和侵袭抑制作用的体外和体内研究 |
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| 引用本文： | 田辉,刘贤锡,张 冰,孙启峰,孙东峰.ODC, AdoMetDC双反义腺病毒对肺癌增殖和侵袭抑制作用的体外和体内研究[J].生物化学与生物物理进展,2007,34(7):709-717. |
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| 作者姓名： | 田辉 刘贤锡 张 冰 孙启峰 孙东峰 |
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| 作者单位： | 山东大学齐鲁医院胸外科 济南250012(田辉，孙启峰，孙东峰)，山东大学医学院分子生物学实验中心 济南250012(刘贤锡，张冰) |
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| 基金项目： | 国家自然科学基金资助项目(30571844).~~ |
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| 摘 要： | 鸟氨酸脱羧酶(ODC)和S-甲硫氨酸脱羧酶(AdoMetDC)是多胺体内合成的2个关键酶.研究腺病毒Ad-ODC-AdoMetDCas介导的ODC和AdoMetDC反义RNA对肺癌多胺合成,细胞增殖以及侵袭的抑制作用.用活细胞计数和流式细胞术分别检测Ad-ODCas和Ad-ODC-AdoMetDCas对肺癌A-549细胞增殖的影响,蛋白质印迹和HPLC方法分别检测腺病毒对肺癌A-549细胞中ODC和AdoMetDC蛋白表达以及胞内多胺含量的抑制作用,TUNEL标记检测法观察Ad-ODC-AdoMetDCas对肺癌细胞凋亡的影响,Matrigel侵袭实验分析腺病毒对肺癌A-549细胞侵袭活性的改变,裸鼠皮下移植瘤模型研究Ad-ODC-AdoMetDCas对体内肺癌生长的抑制作用.实验结果显示,Ad-ODC-AdoMetDCas明显抑制肺癌A-549细胞的增殖,导致细胞凋亡,显著降低肺癌A-549细胞的体外侵袭能力,肺癌A-549细胞感染Ad-ODC-AdoMetDCas后细胞内3种多胺含量都明显降低,Ad-ODC-AdoMetDCas对已形成的裸鼠皮下移植瘤具有明显的抑制作用.实验表明,ODC和AdoMetDC双反义腺病毒具有显著抑制肺癌增殖和侵袭的作用,对于肺癌的防治研究具有一定的前景.
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| 关 键 词： | 鸟氨酸脱羧酶 S-甲硫氨酸脱羧酶 多胺 肺癌 基因治疗 |
| 收稿时间： | 2007/1/31 0:00:00 |
| 修稿时间： | 2007-01-31 |
Adenovirus-mediated Expression of Both Antisense Ornithine Decarboxylase (ODC) and S-adenosylmethionine Decarboxylase(AdoMetDC) Inhibits Lung Cancer Cell Growth And Invasion In vitro and In vivo |
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| Tian Hui,LIU Xian-Xi,ZHANG Bing,SUN Qi-Feng and SUN Dong-Feng.Adenovirus-mediated Expression of Both Antisense Ornithine Decarboxylase (ODC) and S-adenosylmethionine Decarboxylase(AdoMetDC) Inhibits Lung Cancer Cell Growth And Invasion In vitro and In vivo[J].Progress In Biochemistry and Biophysics,2007,34(7):709-717. |
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| Authors: | Tian Hui LIU Xian-Xi ZHANG Bing SUN Qi-Feng and SUN Dong-Feng |
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| Institution: | Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, China;Department of Medicine, Medical Molecular Biology Experimental Center, Shandong University, Jinan 250012, China;Department of Medicine, Medical Molecular Biology Experimental Center, Shandong University, Jinan 250012, China;Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, China;Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, China |
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| Abstract: | Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). Antisense ODC and AdoMetDC sequences were cloned into an adenoviral vector (Ad-ODC-AdoMetDCas). To evaluated the effect of recombinant adenovirus Ad-ODC-AdoMetDCas which can simultaneously express both antisense ornithine decarboxylase (ODC) and sadenosylmethionine decarboxylase (AdoMetDC), the human lung cancer cell line A-549, was infected with Ad-ODC-AdoMetDCas as well as with control vector. Viable cell counting, determination of polyamine concentrations, cell apoptosis, and Matrigel invasion assays were performed in order to assess properties of tumor growth and invasiveness. Furthermore, Ad-ODC-AdoMetDCas's anti-tumor effect was also evaluated in vivo in a nude mice xenograft model. It was demonstrated that adenovirus-mediated ODC and AdoMetDC antisense expression could inhibit tumor cell growth, lead to cell apoptosis and reduce tumor cell invasiveness. Polyamine levels were significantly decreased in Ad-ODC-AdoMetDCas-treated cells compared with controls. This adenovirus also induced tumor regression in established tumors in nude mice. It was suggested that as a new anticancer reagent, the recombinant adenovirus Ad-ODC-AdoMetDCas holds promising hope for the therapy of lung cancers. |
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| Keywords: | ornithine decarboxylase S-adenosylmethionine decarboxylase polyamine lung cancer gene therapy |
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