The present study was designed to investigate the combined effect of fotemustine, a nitrosureas antineoplastic agent along with simvastatin and/or dexamethasone on C6 glioblastoma. The C6 glioblastoma cells (1x10(6)) were inoculated in rat brains. Ten days later, rats were treated with 10 mg kg(-1) fotemustine, 3 mg kg(-1) day(-1) dexamethasone and 3 mg kg(-1) day(-1) simvastatin alone or with their combination. Monoclonal antibody Ki-67 was used to evaluate cell proliferation. The effects of these drug alone or in combination on fatty acid profile of C6 glioblastoma were determined using capillary gas, chromatography. Dexamethasone +/- simvastatin decreased the tumor weight 36-46% (p = 0.001-0.029): The fotemustine+dexamethasone+simvastatin combination was more effective than the drugs given separately in inhibiting the growth of the tumor (33.9-58.5%, p = 0.000). In the fotemustine+dexamethasone+simvastatin group, the total fatty acid amount was high compared with control tumors, whereas low in the fotemustine+simvastatin group (31.95 +/- 1.91 and 16.11 +/- 1.96 mu g mg(-1), p = 0.021). The number of Ki-67 positive cell decreased compared with control tumors by drug therapy except dexamethasone alone. The decrease was greatest in the treatment with fotemustine+dexamethasone+simvastatin (26.5-51.8%, p = 0.000-0.020). These data show that, fotemustine+dexamethasone+simvastatin combination is more effective than fotemustine alone on inhibition of cell proliferation and tumor progression.