Enhancement of antitumor activity of cisplatin on human gastric cancer cells in vitro and in vivo by buthionine sulfoximine.
An attempt was made to evaluate the enhancement of the antitumor activity of cisplatin (DDP) by buthionine sulfoximine (BSO) in vitro and in vivo. In the in vitro study, pre-treatment with BSO (5, 10 and 25 mM) increased the antitumor activity of DDP against the gastric cancer cell lines MKN-28 and MKN-45, whereas BSO alone exhibited only slight antitumor activity (inhibition rate, 20-30%). In the in vivo study, the antitumor effects of DDP against human gastric cancer xenografts St-15 and SC-1-NU in BALB/c nu/nu mice were enhanced pretreatment with BSO, which was administered intraperitoneally at a dose of 500 mg/kg according to a schedule of qd x 3. BSO alone showed no antitumor effects against these tumors in nude mice. The side effects (assessed in terms of death rate and body weight loss) associated with the maximum tolerated dose of DDP (9 mg/kg) were not increased by BSO pretreatment. As BSO increased the antitumor activity of DDP without a corresponding increment of its toxicity, BSO appears to be a promising agent for further study.
Saikawa
Y
Y
Department of Surgery, School of Medicine, Keio University, Tokyo.
Kubota
T
T
Kuo
T H
TH
Furukawa
T
T
Tanino
H
H
Watanabe
M
M
Ishibiki
K
K
Kitajima
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005978:Glutathione / Q000032:analysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin