Background & objective: Esophageal carcinoma is one of the most common malignant tumors in China. It is reported that the content and biosynthesis of polyamine in esophageal cancer is markedly increased. This study was to investigate inhibitory effects of both antisense ornithine decarboxylase (ODCas) and S-adenosylmethionine bi-antisense (AdoMetDCas) on polyamine biosynthesis, cell proliferation and invasion of esophageal cancer cell line Eca109.
Methods: An adenoviral vector Ad-ODC-AdoMetDCas containing antisense sequences of ODCse and AdoMetDCas was used. Cell proliferation was observed by counting viable cells or BrdU labeling. Protein expressions of ODC and AdoMetDC and the polyamine content in Eca109 cells were measured by Western blot and high performance liquid chromatography (HPLC), respectively. Invasion of Eca109 cells in vitro was detected using Matrigel invasion assay. Furthermore, the anti-proliferation effect of Ad-ODC-AdoMetDCas on Eca109 cell xenografts in nude mice was evaluated.
Results: Ad-ODC-AdoMetDCas significantly inhibited proliferation of Eca109 cells(P<0.05) and protein expressions of ODC and AdoMetDC. Transfection of Ad-ODC-AdoMetDCas significantly decreased synthesis of three polyamines in Eca109 cells, which were putrescine (Put), spermidine (Spd) and spermine (Spm) (P<0.05). Ad-ODC-AdoMetDCas dramatically suppressed invasiveness of Eca109 cells in vitro(P<0.05). In addition, compared with Ad-GFP, Ad-ODC-AdoMetDCas significantly suppressed the growth of Eca109 cell xenografts in nude mice.
Conclusion: Ad-ODC-AdoMetDCas significantly inhibits cell proliferation and invasion in esophageal cancer Eca109 cells.