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Antitumor effect of antisense ODC adenovirus on human prostate cancer cells
1Department of Medicine, Medical Molecular Biology Experimental Center, Shandong University, Jinan, China.
Abstract:
Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially prostate cancers. Some chemotherapeutic agents aimed to decrease ODC expression showed inhibitory effects on cancer cells. In this study, we examined the effect of adenoviral-transduced antisense ODC on prostate cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion assay showed relatively low invasion. Marked suppression of tumor formation was observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the antitumor effect on the human prostate cancer cells.
Insights
Adenoviral-transduced antisense ornithine decarboxylase (ODC) significantly reduced ODC expression and polyamine levels in prostate cancer cells. This approach demonstrated potent antitumor effects, inhibiting cell growth and tumor formation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ornithine decarboxylase (ODC) is upregulated in cancer, particularly prostate cancer.
- Targeting ODC expression is a potential chemotherapeutic strategy for cancer treatment.
Purpose of the Study:
- To investigate the antitumor effects of adenoviral-transduced antisense ODC (rAd-ODC/Ex3as) on human prostate cancer cells.
- To evaluate the impact of rAd-ODC/Ex3as on ODC expression, polyamine levels, cell growth, cell cycle, invasion, and tumorigenicity.
Main Methods:
- Adenovirus-mediated gene transfer of antisense ODC into PC-3 and LNCap prostate cancer cells.
- Quantification of ODC expression and polyamine concentrations using Western blotting and HPLC.
- Assessment of cell viability (MTT assay), cell cycle progression (FCM), cellular invasion (Matrigel assay), and in vivo tumor growth (nude mouse xenograft model).
Main Results:
- rAd-ODC/Ex3as treatment reduced ODC expression by 45% in PC-3 and 59% in LNCap cells.
- Significant decrease in intracellular polyamine concentrations observed post-treatment.
- Inhibition of cell proliferation, G1 phase cell cycle arrest, reduced cellular invasion, and marked suppression of tumor formation in vivo.
Conclusions:
- Adenoviral-transduced antisense ODC effectively suppresses prostate cancer cell growth and tumorigenicity.
- rAd-ODC/Ex3as represents a promising therapeutic strategy for prostate cancer treatment by targeting ODC-mediated polyamine biosynthesis.
