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-retin oic acid (RA), difluoromethylornithine (DFMO) and the tripeptide colon mito sis inhibitor (CMI) on the in vivo growth of human colon carcinoma cells (H T-29) in athymic mice. Materials and Methods: DFMO was given as 2 % in the drinking water. RA (400 nmol/animal) and CMI (1 pmol/animal) were administe red i.p. daily. Results: RA, DFMO or CMI given alone, reduced the tumour gr owth by 40-60 % (P < 0.001). When DFMO was given as a standard therapy sign ificant synergism was achieved with RA (P = 0.008). In contrast CMI acted a ntagonistically with DFMO (P = 0.013). DFMO + RA + CMI was not move Effecti ve than DFMO + RA. Without DFMO administration, CMI achieved synergism with RA (P < 0.001). Conclusions: Syne,Synergism was shown between RA and DFMO, and RA and CMI, brit not between CMI and DFMO.