In vivo growth inhibition of human colon carcinoma cells (HT-29) by all-trans-retinoic acid, difluoromethylornithine, and colon mitosis inhibitor, individually and in combination.
BACKGROUND
An important strategy in experimental chemotherapy of cancer is to combine agents with different mechanisms of action in order to achieve enhanced effect by synergism. We studied the combination of all-trans-retinoic acid (RA), difluoromethylornithine (DFMO) and the tripeptide colon mitosis inhibitor (CMI) on the in vivo growth of human colon carcinoma cells (HT-29) in athymic mice.


METHODS
DFMO was given as 2% in the drinking water. RA (400 nmol/animal) and CMI (1 pmol/animal) were administered i.p. daily.


RESULTS
RA, DFMO or CMI given alone, reduced the tumour growth by 40-60% (P < 0.001). When DFMO was given as a standard therapy, significant synergism was achieved with RA (P = 0.008). In contrast, CMI acted antagonistically with DFMO (P = 0.013). DFMO + RA + CMI was not more effective than DFMO + RA. Without DFMO administration, CMI achieved synergism with RA (P < 0.001).


CONCLUSIONS
Synergism was shown between RA and DFMO, and RA and CMI, but not between CMI and DFMO.
Paulsen
J E
JE
Department of Environmental Medicine, National Institute of Public Health, PO Box 4404, Torshov, N-0403, Oslo, Norway. jan.erik.paulsen@folkehelsa.no
Lützow-Holm
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D000518:Eflornithine / Q000008:administration & dosage / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D014212:Tretinoin / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D009842:Oligopeptides; D014212:Tretinoin; C023866:pyroglutamyl-histidyl-glycine; D011761:Pyrrolidonecarboxylic Acid; D000518:Eflornithine