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. Materials and Methods: DFMO was given as 2 % in the drinking water. RA (400nmollanimal) 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.