ALL-TRANS-RETINOIC ACID INHIBITS GROWTH OF HUMAN PANCREATIC-CANCER CELL-LINES

Retinoids are a class of molecules structurally related to vitamin A t hat have potent antiproliferative and differentiating effects on a var iety of normal and neoplastic tissues. All-trans-retinoic acid (ATRA) has become a first-line chemotherapeutic agent in the treatment of cer tain leukemias; however, the effect of ATRA on pancreatic tumors is un known. The purpose of this study was to determine the effect of ATRA o n the growth characteristics of both exocrine and endocrine human panc reatic cancer cell lines. The in vitro growth of four cell lines was e xamined 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 pancre atic carcinoid (BON) xenografts in Balb/c athymic mice was determined by treatment with several doses of ATRA over 1 month. The growth of BO N tumors was inhibited in a dose-dependent fashion. These results sugg est that ATRA exerts direct antiproliferative effects on both exocrine and endocrine human pancreatic cancers and may be useful in the chemo therapy of these tumors.