Modulation of murine neuroblastoma in nude mice by opioid antagonists.
Naltrexone, an opioid antagonist, had an inhibitory effect on the growth of murine S20Y neuroblastoma in BALB/c nude mice. Daily injections of 0.1 mg naltrexone/kg, which invoked a receptor blockade for 6-8 hours/day, resulted in 31-92% delay in latency time prior to tumor expression and a 27-49% increase in mean survival time; the magnitude of antitumor response was governed by tumor burden. Inoculation of neuroblastoma (10(6)-2.5 X 10(4) cells) resulted in measurable tumors in 10-13 days and mean survival times of 30-34 days. Immunoreactive beta-endorphin was detected in tumor tissue (39.7 pg/mg protein). Receptor binding assays revealed specific saturable binding of ligands related to delta- and kappa-binding sites, but not for the mu-binding site. These results demonstrate that opioid antagonist modulation of neuro-oncogenesis is not dependent on the integrity of T-cell-mediated immunity and suggest the feasibility of utilizing the nude mouse model in exploring the role of endogenous opioids in human cancers.
D000818:Animals; D004195:Disease Models, Animal / Q000276:immunology; D004723:Endorphins / Q000032:analysis; D006085:Graft Survival / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009271:Naltrexone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000032:analysis / Q000276:immunology* / Q000517:prevention & control; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D001615:beta-Endorphin
D004723:Endorphins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D001615:beta-Endorphin