Experimental Study Of The Inhibitory Effect On Lung Cancers By Adenoviral-Mediated Gene Transfer Of Antisense ODC

The polyamines, spermidine, spermine and the diamine precursor, putrescine, are positively charged aliphatic amines at physiological conditions, have a low-molecular weight and a simple chemical structure. Polyamines are known to be critically involved in cell growth and have been implicated in the process of cell transformation. On the other hand, the level of polyamine is high in cancer cell and tissues, and rapid tumor growth has been associated with remarkable elevation of polyamine biosynthesis and accumulation. Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells especially lung cancers. Some chemotherapeutic agents, such as DFMO, which aimed to inhibit the activity of ODC have appeared and taken on inhibitory effects on tumor growth in vitro and in vivo, though showing dose-limiting toxicity. Taken together, these findings suggest that ODC may provide an important target for the development agents that inhibit carcinogenesis and tumor growth.Lung cancer is the most frequently diagnosed cancer in the world. Metastatic lung cancer is essentially resistant to systemic cytotoxic chemotherapy, while external beam and radioisotope radiotherapy offers only symptom palliation. Clearly the development of novel therapies, such as gene therapy, is a high priority. Some studies had proved that lung carcinomas had greater elevated polyamine levels and that the expression of ODC was greater in the lung cancer than in normal lung tissues.