EFFECTS OF DEMO ON GLIOMA CELL-PROLIFERATION, MIGRATION AND INVASION IN-VITRO

The polyamine inhibitor DL-alpha-difluoromethylornithine (DFMO) is a s pecific irreversible inhibitor of ornithine decarboxylase which is a r ate-limiting enzyme in the polyamine bio-synthesis pathway. The presen t study describes the effects of DFMO on glioma cell proliferation, mi gration and invasion using multicellular spheroids from three glioma c ell lines (GaMg, U-251 Mg and U-87 Mg). 10 mM DFMO reduced cell migrat ion in the three cell lines by about 30-50%. 1 mM putrescine, added to gether with DFMO inhibited the DFMO effect. A stronger effect was obse rved in the growth assay where 10 mM DFMO reduced the spheroid growth, for all cell lines, by 90%. This effect was also reversed by adding 1 mM of putrescine. In vitro tumor cell invasion experiments indicated after 3 days of confrontation, an extensive invasion also after 10 mM DFMO treatment. The brain aggregate volumes were reduced to about the same extent as in the absence of drug, suggesting essentially no effec ts of DFMO on the invasive process. It is concluded that the tumor sph eroids retained their ability to invade normal brain tissue even after DFMO exposure. However, DFMO inhibited spheroid growth and cell migra tion which supports the notion that cell growth, migration and invasio n are biological properties that are not necessarily related to each o ther.