Antitumor effect of alpha-difluoromethylornithine (DFMO) changes in ornithine decarboxylase (ODC) activity and polyamine (PA) levels in human tumor transplanted into nude mice

Three human carcinoma xenografts serially transplanted into nude mice were used for the study of antitumor effect of DFMO. One breast carcinoma (MX-1) and two colon carcinomas (Exp-42, Co-3) were inoculated into the subcutaneous tissue of BALB/c nude mice. When the tumor weights reached 100 -300mg, 0.5%, 1% and 2% DFMO was administrated ad libitum in tap water for 21 days, MMC was administrated ip q7d x 3(DAY 0, 7,14) at 0.5mg/kg or 2.0mg/kg. Combination of 1% DFMO and MMC 1mg/kg x 3 using a similar schedule was also made. After 21 days, the tumors were weighed and assays of ODC activity and analysis of PA in the tumors were done. The antitumor effects (the lowest value of TRW/CRW) of 2% DFMO against MX-1, Exp-42 and Co-3 were 4.83%, 35.8% and 73.4% respectively. Synergic effects of MMC were observed in all three tumors. With 2% DFMO, ODC and PUT levels were decreased to 16.4%, 2.89% of control in MX-1, 14.8%, 6.62% in Exp-42, 4.18%, 11.2% in Co-3 respectively. Of MX-1 and Exp-42, the dose of DFMO administrated, the antitumor effect and the PUT levels were correlated (p less than 0.05). DFMO is one of the potent chemotherapeutic agents and may be useful in combination chemotherapy.