Combined therapy of polyamine antimetabolites and antitumor drugs for human gastric cancer xenotransplanted into nude mice

• Published in: Japanese journal of surgery 1986-03, Vol.16 (2), p.133-139
• Main Authors: Fujimoto, S, Igarashi, K, Shrestha, R D, Miyazaki, M, Endoh, F, Ohta, M, Togawa, Y, Okui, K
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Body Weight - drug effects; Carcinoma - drug therapy; Eflornithine; Floxuridine - administration & dosage; Fluorouracil - administration & dosage; Mice; Mice, Inbred BALB C; Mice, Nude; Mitoguazone - administration & dosage; Neoplasm Transplantation; Nimustine; Nitrosourea Compounds - administration & dosage; Ornithine - administration & dosage; Ornithine - analogs & derivatives; Stomach Neoplasms - drug therapy
• ISSN: 0047-1909; 1436-2813
• DOI: 10.1007/BF02471083

Antitumor therapies using polyamine antimetabolites combined with 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3(2-chloroethyl)-3-nitrosourea (ACNU) or fluorinated pyrimidines for human gastric cancer xenotransplanted into nude mice were studied to determine inhibiting post-therapeutic regrowth of the tumor after cessation of antitumor treatments with polyamine antimetabolites alone. ACNU 20 mg/kg, fluorinated pyrimidine, 5-FU 52.8 mg/kg and 5'-deoxy-5-fluorouridine (5'-DFUR) 100 mg/kg as well as polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) 1000 mg/kg and methylglyoxal-bis-guanylhydrazone (MGBG) 50 mg/kg were given intraperitoneally for 5 successive days. When DFMO and MGBG were combined with ACNU, the post-therapeutic regrowth was definitely inhibited, while combined treatments with 5-FU or 5'-DFUR did not inhibit the regrowth. Post-therapeutic DNA biosynthesis was suppressed in mice given DFMO, MGBG plus ACNU. On the contrary, in mice treated with DFMO, MGBG plus 5-FU or 5'-DFUR, suppression of DNA biosynthesis was not observed. Tumor tissue spermine levels in the DFMO, MGBG plus 5-FU or 5'-DFUR group remained unchanged, compared to those in the DFMO + MGBG group. In mice given DFMO, MGBG plus ACNU, however, spermine levels were markedly depressed; and the ACNU alone depressed also the tissue spermine levels. These different results between nitrosourea and fluorinated pyrimidines may relate to mechanisms of action of these antitumor drugs.