OPIOID GROWTH-FACTOR (OGF) INHIBITS HUMAN PANCREATIC-CANCER TRANSPLANTED INTO NUDE-MICE

Nude mice inoculated with human pancreatic cancer (BxPC-3) cells and r eceiving 5 mg/kg of opioid growth factor ([Met(5)]enkephalin; OGF) thr ee times daily exhibited a marked retardation in tumorigenicity compar ed to animals injected with sterile water (controls). OGF-treated anim als had a delay of 43% in initial tumor appearance compared to control subjects (10.6 days). At the time when all of the control mice had tu mors, 62% of the mice in the OGF group had no signs of neoplasia. Tumo r tissue excised from mice after 30 days was assayed for levels of [Me t(5)]enkephalin and zeta opioid receptors, Tumor tissue levels of [Met (5)]enkephalin were 24-fold greater in OGF-treated mice than controls, but plasma levels of OGF were 8.6-fold lower in animals receiving OGF . Specific and saturable binding of radiolabeled [Met(5)]enkephalin to nuclear homogenates of pancreatic tumor tissue was recorded, with a b inding affinity (K-d) of 10 nM and a binding capacity (B-max) of 46.8 fmol/mg protein. Binding capacity, but not affinity, of [H-3 Met(5)]en kephalin was reduced by 58% of control levels in tumor tissue from mic e of the OGF group. OGF and the zeta (zeta) opioid receptor were detec ted in human pancreatic tumor cells by immuno-cytochemistry. These res ults demonstrate that an endogenous opioid and its receptor are presen t in human pancreatic cancer, and act as a negative regulator of tumor igenesis in vivo. (C) 1997 Elsevier Science Ireland Ltd.