Opioid growth factor (OGF) inhibits human pancreatic cancer transplanted into nude mice.
Nude mice inoculated with human pancreatic cancer (BxPC-3) cells and receiving 5 mg/kg of opioid growth factor ([Met5]enkephalin; OGF) three times daily exhibited a marked retardation in tumorigenicity compared to animals injected with sterile water (controls). OGF-treated animals 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 tumors, 62% of the mice in the OGF group had no signs of neoplasia. Tumor tissue excised from mice after 30 days was assayed for levels of [Met5]enkephalin and zeta opioid receptors. Tumor tissue levels of [Met5]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 [Met5]enkephalin to nuclear homogenates of pancreatic tumor tissue was recorded, with a binding affinity (Kd) of 10 nM and a binding capacity (Bmax) of 46.8 fmol/mg protein. Binding capacity, but not affinity, of [3H-Met5]enkephalin was reduced by 58% of control levels in tumor tissue from mice of the OGF group. OGF and the zeta (zeta) opioid receptor were detected in human pancreatic tumor cells by immuno-cytochemistry. These results demonstrate that an endogenous opioid and its receptor are present in human pancreatic cancer, and act as a negative regulator of tumorigenesis in vivo.
Zagon
I S
IS
Department of Neuroscience and Anatomy, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA. iszl$@psuvm.psu.edu
Hytrek
S D
SD
Smith
J P
JP
McLaughlin
P J
PJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004744:Enkephalin, Methionine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011863:Radioimmunoassay; D011957:Receptors, Opioid / Q000032:analysis; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D011957:Receptors, Opioid; C062922:zeta receptor; D004744:Enkephalin, Methionine