标题：Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus
作者：Wang, Wei;Jin, Bin;Li, Wei;Xu, Chun-Xiao;Cui, Fu-Ai;Liu, Bin;Yan, Yun-Fei;Liu, Xian-Xi;Wang, Xiu-Li .
作者机构：[Wang, W] Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China;[ Jin, B] Department of Genera 更多
通讯作者地址：[Liu, XX]Shandong Univ, Inst Biochem & Mol Biol, Sch Med, Jinan 250012, Peoples R China.
来源：Molecular biology reports
关键词：polyamine: biosynthesis;ornithine decarboxylase: 9024-60-6;expression;EC 220.127.116.11;cell proliferation;cell growth;cell invasiveness
摘要：The expression of Ornithine decarboxylase (ODC) which is the first key enzyme of polyamine biosynthesis is increased in cancer cells. We had blocked the polyamine synthesis pathway using the adenoviral-mediated antisense ODC in some cancer cells such as prostate cancers and colorectal cancers. These researches demonstrated that ODC antisense expression could inhibit tumor cell growth. In order to reach the goal of applying the targeting gene therapy in clinical practice, we cloned the antisense ODC RNA which was driven by cancer specific promoter ( hTERT promoter; telomerase reverse transcriptase promoter) into the adenovirus vector (rAd-CMV-GFP-hTERTp-ODC). Human cancer cell lines (HepG2, Bel-7402, A549) and normal cell lines (HELF, LO2) were infected separately with rAd-CMV-GFP-hTERTp-ODC as well as with control vector (rAd-CMV-GFP). Luciferase activity assay was performed to determine hTERT promoter activity. Cell growth curves analysis, western blot analysis, flow cytometry analysis and Matrigel invasion assays were performed to assess properties of cell growth and invasiveness. The results showed that there was significant inhibition of ODC expression and cell proliferation in cancer cells treated with rAd-CMV-GFP-hTERTp-ODC compared with cells treated with PBS or rAd-CMV-GFP, and no significant inhibition was detected in normal cells. Our research offers a powerful and safe new therapeutic strategy for cancer targeted treatment.