Tian Hui, Liu Xianxi, Zhang Bing, Sun Qifeng, Sun Dongfeng
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, China.
Acta Biochim Biophys Sin (Shanghai). 2007 Jun;39(6):423-30. doi: 10.1111/j.1745-7270.2007.00294.x.
Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). Antisense sequences of ODC and AdoMetDC genes were cloned into an adenoviral vector (named Ad-ODC-AdoMetDCas). To evaluate the effects of recombinant adenovirus Ad-ODC-AdoMetDCas that can simultaneously express both antisense ODC and AdoMetDC, the human lung cancer cell line A-549 was infected with Ad-ODC-AdoMetDCas or the control vector. Viable cell counting, determination of polyamine concentrations, cell cycle analysis, and Matrigel invasion assays were carried out to assess the properties of tumor growth and invasiveness. Our study showed that adenovirus-mediated antisense ODC and AdoMetDC expression inhibits tumor cell growth through blocking the polyamine synthesis pathway. Tumor cells were arrested at the G1 phase after gene transfer and the invasiveness was reduced. It suggested that the recombinant adenovirus Ad-ODC-AdoMetDCas might be a new anticancer reagent in the treatment of lung cancers.
多胺生物合成主要受鸟氨酸脱羧酶（ODC）和S-腺苷甲硫氨酸脱羧酶（AdoMetDC）调控。将ODC和AdoMetDC基因的反义序列克隆到腺病毒载体中（命名为Ad-ODC-AdoMetDCas）。为评估可同时表达反义ODC和AdoMetDC的重组腺病毒Ad-ODC-AdoMetDCas的作用，用人肺癌细胞系A-549感染Ad-ODC-AdoMetDCas或对照载体。进行活细胞计数、多胺浓度测定、细胞周期分析和基质胶侵袭试验以评估肿瘤生长和侵袭特性。我们的研究表明，腺病毒介导的反义ODC和AdoMetDC表达通过阻断多胺合成途径抑制肿瘤细胞生长。基因转移后肿瘤细胞停滞于G1期，侵袭性降低。这表明重组腺病毒Ad-ODC-AdoMetDCas可能是治疗肺癌的一种新型抗癌试剂。
