Lentiviral Vector-mediated Down-regulation Of Ornithine Decarboxylase Inhibit Tumor Cell Growth In Vitro And In Vivo

Polyamines are present in all living cells, prokaryotes, eukaryotes, plants and animals. In mammalian cells, the natural polyamines—putrescine, spermidine and spermine —are found in millimolar concentrations. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several type cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide, polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer.Ornithine decarboxylase (ODC) is the first enzyme in the polyamine synthesis pathway. A possible role for ODC in tumor cell growth has been suggested by a series of studies and the overexpression of ODC in NIH 3T3 cells caused transformation of these cells to a malignant phenotype, in essence qualifying ODC as an oncogene. An increase in ODC activity is one of the earliest biochemical events associated with the induction of cellular proliferation, and depletion of polyamines by DL - a -difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ODC, attenuates tropic responses in a number of tissues. We hypothesized that downregulation of ODC may inhibit the proliferation of tumor cells.Colorectal cancer is the fourth most common form of cancer in the world. In spite of improvements in detection and chemotherapy, there are still...