Downregulation of ornithine decarboxylase by pcDNA-ODCr inhibits gastric cancer cell growth in vitro.
Ornithine decarboxylase (ODC), the first rate-limiting enzyme of polyamine biosynthesis, was found to be associated with cell growth, proliferation and transformation. ODC gene expression in gastric cancer was increased and its level was positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. In order to evaluate the therapeutic effects of antisense RNA of ODC on gastric cancer, an antisense RNA of ODC expressing plasmid pcDNA-ODCr which delivered a 120 bp fragment complementary to the initiation codon of ODC gene was constructed and transfected to gastric cancer cells SGC7901 and MGC803. Expression of ODC in gastric cancer cells was determined by western blot. Cell proliferation was assessed by MTS assay. Cell cycle was analyzed by flow cytometry and Matrigel assay was performed to assess the ability of gastric cancer cell invasiveness. The results showed that the ODC gene expression in gastric cancer cells transfected with the pcDNA-ODCr was downregulated efficiently. Tumor cell proliferation was suppressed significantly, and cell cycle was arrested at G1 phase. Gastric cancer cells had reduced invasiveness after gene transfer. Our study suggested that antisense RNA of ODC expressing plasmid pcDNA-ODCr had antitumor activity by inhibiting the expression of ODC, and downregulation of ODC expression using a gene therapy approach might be a novel therapeutic strategy for gastric cancer.
Xu
Chun-xiao
CX
Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, China.
Yan
Yun-fei
YF
Yang
Ya-pei
YP
Liu
Bin
B
Xin
Jia-xuan
JX
Chen
Shi-min
SM
Wang
Wei
W
Jiang
Chun-ying
CY
Lu
Zhao-xin
ZX
Liu
Xian-xi
XX
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007797:Laminin / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000235:genetics; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010957:Plasmids / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000628:therapy*
D004338:Drug Combinations; D007797:Laminin; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; C059485:matrigel; D012313:RNA; D003094:Collagen; D009955:Ornithine Decarboxylase