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Published on: January 19, 2019
Antitumor effect of antisense ornithine decarboxylase adenovirus on human lung cancer cells
Hui Tian1, Lin Li, Xian-Xi Liu
1Department of Thoracic Surgery, Shandong University Qi Lu Hospital, Jinan 250012, China. tianhuiy@ sohu.com
Abstract:
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.
Insights
Antisense Ornithine Decarboxylase (ODC) delivered via adenovirus significantly inhibited lung cancer cell growth. This approach reduced ODC expression and polyamine levels, inducing substantial cancer cell apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Ornithine decarboxylase (ODC) is upregulated in cancer, particularly lung cancer.
- Targeting ODC gene expression shows promise for cancer chemotherapy.
- Polyamines, regulated by ODC, are crucial for cell proliferation.
Purpose of the Study:
- To investigate the antitumor effects of adenoviral-transduced antisense ODC (rAd-ODC/Ex3as) on human lung cancer cells.
- To assess the impact of rAd-ODC/Ex3as on ODC expression, polyamine levels, cell growth, and apoptosis.
Main Methods:
- Adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was used to infect A-549 lung cancer cells.
- Cell viability was assessed using the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay.
- ODC expression and polyamine concentrations were quantified via Western blot and HPLC.
- Apoptosis was analyzed using Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL).
Main Results:
- rAd-ODC/Ex3as treatment reduced ODC expression by 54% in A-549 cells.
- Concentrations of three key polyamines were significantly decreased post-treatment.
- Cell growth was substantially inhibited, and apoptosis was induced with an index of 46%.
Conclusions:
- Adenoviral-mediated antisense ODC delivery effectively suppresses lung cancer cell proliferation.
- rAd-ODC/Ex3as demonstrates significant antitumor activity against human lung cancer cells.
- Targeting ODC via gene therapy represents a potential therapeutic strategy for lung cancer.