INHIBITION OF HUMAN COLON-CANCER BY INTERMITTENT OPIOID RECEPTOR BLOCKADE WITH NALTREXONE

Nude mice inoculated with human colon cancer (HT-29) and receiving 0.1 mg/kg naltrexone (NTX) beginning immediately after tumor cell injecti on exhibited a marked retardation in tumorigenicity. This dosage of NT X, which blocked opioid receptors for 6-8 h/day, resulted in a delay o f 2.4-fold in tumor appearance compared to control subjects. At the ti me (10 days) when all control mice had tumors, 80% of the mice in the 0.1 mg/kg NTX group had no signs of neoplasia. Binding capacity, but n ot affinity, of [H-3][Met(5)]-enkephalin was reduced 85% of control le vels in tumor tissue from mice of the 0.1 NTX group. Plasma, but not t umor tissue levels of [Met(5)]-enkephalin were elevated (2.5-fold) in contrast to control values, These results suggest that daily intermitt ent opioid receptor blockade with NTX provokes the interaction of opio ids and receptors in the interval following drug availability, with op ioids serving to inhibit tumorigenicity of human colon cancer.