Antitumor effects of two polyamine antimetabolites combined with mitomycin C on human stomach cancer cells xenotransplanted into nude mice.

The antitumor effects of alpha-difluoromethylornithine (DFMO), methylglyoxal-bis-guanylhydrazone (MGBG) and mitomycin C (MMC), administered separately or in various combinations, on human stomach cancer cells xenotransplanted into BALB/c nude mice were studied using the protocol of Battelle's Columbus Laboratories (Ovejera et al., 1978). DFMO (1,000 mg/kg in 2 divided doses) and MGBG (50 mg/kg) were given intraperitoneally (i.p.) for 7 consecutive days from the time when the tumor weighed about 100 mg. MMC (2 mg/kg) was given i.p. every other day from the same time. Animals treated with either DFMO or MGBG alone displayed tumor growth comparable to that seen in untreated controls. In mice treated with DFMO plus MGBG with or without MMC, or in mice treated only with MMC, tumor growth was significantly lower than in untreated mice. In the group which received only combined DFMO/MGBG there was a rapid regrowth of the tumor after termination of therapy. Tumor putrescine levels decreased within 4 days following the administration of DFMO; however, spermidine levels did not decline with either DFMO or MGBG treatment even after 7 days. When combined DFMO/MGBG was given, there was a significant decline in spermidine levels 7 days after the initiation of treatment. In contrast, when MMC alone was administered, putrescine and spermidine levels in the tumor did not differ from those in control mice. Spermine decreased markedly in tumor with the combined administration of DFMO/MGBG as well as with combined DFMO/MGBG/MMC, but decreased only slightly when MMC alone or MMC plus either DFMO or MGBG was administered. By the 7th treatment day, DNA biosynthesis in the tumor had dropped markedly in all groups except those receiving DFMO or MGBG alone.