Antitumor effect of antisense ornithine decarboxylase adenovirus on human lung cancer cells.
Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially lung cancer cells. Some chemotherapeutic agents aimed at decreasing ODC gene expression showed inhibitory effects on cancer cells. In this study, we examined the effects of adenoviral transduced antisense ODC on lung cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was used to infect lung cancer cell line A-549. The 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to analyze the effect on cell growth. Expression of ODC and concentration of polyamines in cells were determined by Western blot analysis and high performance liquid chromatography. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling was used to analyze cell apoptosis. The expression of ODC in A-549 cells was reduced to 54%, and that of three polyamines was also decreased through the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling showed that rAd-ODC/Ex3as could lead to cell apoptosis, with apoptosis index of 46%. This study suggests that rAd-ODC/Ex3as has an antitumor effect on the human lung cancer cells.
Tian
Hui
H
Department of Thoracic Surgery, Shandong University Qi Lu Hospital, Jinan 250012, China. tianhuiy@ sohu.com
Li
Lin
L
Liu
Xian-Xi
XX
Zhang
Yan
Y
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000737:chemistry / Q000235:genetics*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D016376:Oligonucleotides, Antisense; D013778:Tetrazolium Salts; D013844:Thiazoles; D001710:Biotin; D009955:Ornithine Decarboxylase; C022616:thiazolyl blue