Differential and antagonistic effects of 9-cis-retinoic acid and vitamin Danalogues on pancreatic cancer cells in vitro

Retinoids and Vitamin D are known to exert important anti-tumour effects in a variety of cell types. In this study the effects of 9-cis-retinoic acid (9cRA) the vitamin D analogues EB1089 and CB1093 on three pancreatic adenoc arcinoma cell lines were investigated. All compounds caused inhibition of i n vitro growth but the vitamin D analogues were generally the more potent g rowth inhibitors. They were also more effective on their own than in combin ation with 9cRA. Growth arrest correlated with an increased proportion of c ells in the G0/G1 phase. Apoptosis was induced in the three cell lines by 9 cRA, whereas neither EB1089 nor CB1093 had this effect. Furthermore, additi on of EB1089 or CB1093 together with 9cRA resulted in significantly reduced apoptosis. Our results show that retinoic acids as well as vitamin D analo gues have inhibitory effects on pancreatic tumour cells but different and a ntagonistic mechanisms seem to be employed. (C) 2000 Cancer Research Campai gn.