Combined effect of 5-fluorouracil and carboplatin against human gastric cancer cell lines in vitro and in vivo.
The antitumor activity of a sequential combination of 5-fluorouracil (5-FU) and carboplatin (JM-8) was evaluated using gastric cancer cell lines in vitro and in vivo. In the in vitro study, the sequence of 5-FU followed by JM-8 showed higher antitumor activity than that of the reverse sequence. The sequence of 5-FU at 5 micrograms/ml for 24 h followed by 5 micrograms/ml JM-8 for 24 h showed antitumor activity almost equivalent to that of 10 micrograms/ml 5-FU for 24 h and higher activity than that of 10 micrograms/ml JM-8 for 24 h on two cell lines. To evaluate the antitumor activity and toxicity of 5-FU and JM-8 in vivo, BALB/cA nu/nu mice bearing human gastric cancer xenografts St-15, St-40 and SC-1-NU were administered 5-FU and JM-8 intraperitoneally. The sequence of 5-FU prior to JM-8 showed higher antitumor activity than that of the reverse sequence on all the xenografts, and simultaneous administration of 5-FU and JM-8 showed the most potent antitumor activity on St-40 and SC-1-NU. On the other hand, the sequence of 5-FU before JM-8 showed the lowest toxicity in all the treated groups, in terms of death rate, body weight loss and spleen weight loss. This combination is thought to be a promising chemotherapy regimen, showing high antitumor activity without an increment of toxicity.
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Y
Y
Saikawa
T
T
Kubota
T H
TH
Kuo
H
H
Tanino
S
S
Kase
T
T
Furukawa
M
M
Watanabe
K
K
Ishibiki
M
M
Kitajima
R M
RM
Hoffman
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016190:Carboplatin; D005472:Fluorouracil