Adenovirus-mediated expression of both antisense ornithine decarboxylase and S-adenosylmethionine decarboxylase inhibits lung cancer cell growth.
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.
Tian
Hui
H
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, China. tianhuiy@sohu.com
Liu
Xianxi
X
Zhang
Bing
B
Sun
Qifeng
Q
Sun
Dongfeng
D
D012437:Adenosylmethionine Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004338:Drug Combinations; D016193:G1 Phase / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism; D014162:Transfection / Q000379:methods; D019076:Transgenes; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D020319:Oligodeoxyribonucleotides, Antisense; D011073:Polyamines; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D008156:Luciferases; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase