Potent antitumor effect of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine on peritoneal dissemination models of gastrointestinal cancers.
We investigated the antitumor activity of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC) in peritoneal dissemination models of gastrointestinal cancers. Oral administration of 4'-thio-FAC showed a marked effect on the development of ascites and on the survival of nude mice implanted with the highly metastatic MKN-45-P gastric cancer cells into the peritoneal cavity. The toxic effect was observed at a dose of 15 mg/kg, however, no toxicity was observed at a dose of 10 mg/kg with excellent antitumor activity. We established another highly metastatic cell line HCT-15-P by serial intraperitoneal passage of the colon cancer cell line HCT-15. In the HCT-15-P model, 4'-thio-FAC showed an inhibitory effect of peritoneal dissemination and an increase in the life span at a dose of 10 mg/kg. On the other hand, oral administration of 5-fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR) did not show an increase in the life span of mice at a dose of 10 mg/kg. In conclusion, 4'-thio-FAC is a promising therapeutic agent for use against peritoneal dissemination of gastrointestinal cancers.
Miura
Shinji
S
Biochemicals Division, Yamasa Corporation, Choshi, Chiba 288-0056, Japan. miura@yamasa.com
Endo
Yoshio
Y
Yoshimura
Yuichi
Y
Endo
Mikari
M
Yonemura
Yutaka
Y
Sasaki
Takuma
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005467:Floxuridine / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C114001:1-(2-deoxy-2-fluoro-4-thio-arabinofuranosyl)cytosine; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005467:Floxuridine; D003561:Cytarabine; D005472:Fluorouracil