J E Paulsen1, C Lützow-Holm. 1. Department of Environmental Medicine, National Institute of Public Health, PO Box 4404, Torshov, N-0403, Oslo, Norway. jan.erik.paulsen@folkehelsa.no
Abstract
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 (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.
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 tripeptidecolon mitosis inhibitor (CMI) on the in vivo growth of humancolon carcinoma cells (HT-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 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.
Authors: Yannick D Benoit; Kristian B Laursen; Mavee S Witherspoon; Steven M Lipkin; Lorraine J Gudas Journal: J Cell Physiol Date: 2013-04 Impact factor: 6.384