Effect of polyamine deprivation on the survival of intracranial glioblastoma bearing rats

Abstract

It has previously been shown that systematic polyamine deprivation results in the almost complete inhibition of the growth of several solid tumors. The same polyamine deficient diet (containing antibiotics for the decontamination of the gastrointestinal tract, the ornithine decarboxylase inhibitor 2-(difluoromethyl)ornithine, and the polyamine oxidase inhibitor N1, N4-bis-(2,3-butadienyl)putrescine; "drug-containing polyamine deficient chow", DC-PDC) was applied for the first time to the treatment of rats with an intracranial tumor. Rats received intracortical grafts of C6 rat glioblastoma cells, and the length of their survival was determined. Treatment with DC-PDC, starting four days after tumor cell inoculation, significantly prolonged the median survival of the glioblastoma-bearing rats. The results underline the general growth inhibitory effect of systematic polyamine deprivation. Since the effect of polyamine restriction on tumor growth is reversible, combinations with cytotoxic drugs have to be found which exploit the changed functions of polyamine deficient tumor cells.