Lentiviral vector-mediated downregulation of ornithine decarboxylase inhibits tumor cell growth in vitro and in vivo.

Ornithine decarboxylase (ODC), a molecule that is overexpressed in various cancers, has been associated with cell growth and proliferation. Downregulation of ODC may inhibit tumor cell growth. To verify this hypothesis, ODC gene silencing was studied in colorectal cancer cells in vitro and in vivo. A lentiviral system harboring both enhanced green fluorescent protein reporter gene and the ODC short hairpin RNA expression cassette was firstly constructed. Then the stable ODC gene silencing cell lines HT29/ODC and LoVo/ODC were established and their growth-inhibiting characteristics were identified. Real-time RT-PCR analysis of mRNA and Western blot analysis of proteins were used to evaluate the expression of the ODC gene. In the cells studied, ODC expression was significantly decreased. Proliferation of HT29/ODC and LoVo/ODC cells was obviously retarded. In animal experiments, HT29/ODC and LoVo/ODC cell xenografts demonstrated growth suppression compared to parental or control colorectal cancer cell xenografts. The results demonstrated that lentiviral vector was capable of downregulating ODC, resulting in impressive anticancer effects. It offers a powerful new strategy for cancer gene therapy and may be useful in the control of solid tumors, such as human colorectal carcinomas. Copyright (c) 2006 S. Karger AG, Basel.