All-trans-retinoic acid inhibits growth of human pancreatic cancer cell lines

Retinoids are a class of molecules structurally related to vitamin A that have potent antiproliferative and differentiating effects on a variety of normal and neoplastic tissues. All-trans-retinoic acid (ATRA) has become a first-line chemotherapeutic agent in the treatment of certain leukemias; however, the effect of ATRA on pancreatic tumors is unknown. The purpose of this study was to determine the effect of ATRA on the growth characteristics of both exocrine and endocrine human pancreatic cancer cell lines. The in vitro growth of four cell lines was examined after treatment with a wide dose range of ATRA. The growth of all tumor cell lines was inhibited by ATRA in a dose-dependent fashion beginning at 0.1 mu M. The in vivo growth of functioning human pancreatic carcinoid (BON) xenografts in Balb/c athymic mice was determined by treatment with several doses of ATRA over 1 month. The growth of BON tumors was inhibited in a dose-dependent fashion. These results suggest that ATRA exerts direct antiproliferative effects on both exocrine and endocrine human pancreatic cancers and may be useful in the chemotherapy of these tumors.