Different effects of sequential combinations of N-methylformamide with 5-fluorouracil on human colon carcinoma cells growing in nude mice.
The effects of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on tumor growth and morphological features of human colon carcinoma cells (HT29) implanted in nude mice were assessed. Both agents were administered i.p. at tolerable doses: 5-FU at 19 mg/kg for 5 days and NMF at 200 mg/kg for 12 days. Four main schedules were tested: 5-FU alone, NMF alone, NMF followed by 5-FU and 5-FU followed by NMF. The last sequence was the most effective, as compared with the other treatment regimens. In particular, the 5-FU----NMF combination induced a tumor inhibition of about 75% at the end of the treatments (17th day) versus an inhibition of 23%-43% in the other schedules. Morphological observations, carried out by light and electron microscopy, indicated a possible relationship between the presence of structural changes and tumor growth inhibition. The results of this study renew interest in the use of NMF in sequential combination confirming sequence as a critical factor for the optimal combination of NMF and 5-FU.
Arancia
G
G
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Leonetti
C
C
Malorni
W
W
Greco
C
C
Formisano
G
G
Marangolo
M
M
Zupi
G
G
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D005559:Formamides / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005559:Formamides; D005472:Fluorouracil; C002950:methylformamide