[Antitumor efficacy of polyamine antimetabolites and mitomycin C under polyamine-free diet]

Abstract

Treatment of nude mice xenografted with human gastric cancer was carried out by polyamine antimetabolites combined with mitomycin C (MMC) and polyamine-free diet. Polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and ethylglyoxal-bis-guanylhydrazone (EGBG), were given ip in a daily dose of 1,000 mg/kg and 20 mg/kg, respectively, for 6 consecutive days. MMC 2.0 mg/kg was administered every other day. The polyamine-free diet was given from 4 days before start of the treatment through the end of the study. Although the tumor growth rate of the control group given polyamine-free diet was similar to that given normal diet, in the mice treated with EGBG, DFMO plus MMC, the antitumor effect in the polyamine-free diet group was superior to the normal diet group. In comparison with tumor growth suppression due to EGBG plus DFMO or MMC only, the polyamine-free diet group showed better result than the normal diet group to some extent. In mice treated with EGBG, DFMO plus MMC, tumor tissue spermine levels in the polyamine-free diet group were significantly depressed, compared to the normal diet group. Furthermore, marked suppression of DNA biosynthesis was observed in mice given EGBG, DFMO plus MMC together with the polyamine-free diet. These results suggest that combined treatments of polyamine antimetabolites and MMC revealed a marked enhancement of antitumor effects, under conditions of polyamine depletion, which may be responsible for the alteration in DNA structure.