Opioid growth factor (OGF), [Met5]-enkephalin, interacts with the OGF receptor (OGFr) to inhibit the growth of human squamous cell carcinoma of the head and neck (SCCHN) in vitro. Administration of OGF by daily intraperitoneal injection (i.p.) to animals with xenografts of CAL-27, a poorly differentiated SCCHN, is known to repress tumorigenic events. In this study, the ubiquity of OGF action on SCCHN was investigated by examination of OGF activity on SCC-1 tumors; this human cell line is well-differentiated and highly invasive. Mice receiving daily i.p. injections (10 mg/kg) of OGF had more than a 3-day delay in tumor appearance, and decreases in tumor volume ranging from 51 to 64% in comparison to controls throughout the experimental period. Receptor binding analysis for OGFr showed that binding capacity (Bmax) was 2.2-fold greater than control values, but binding affinity (Kd) was comparable. Plasma OGF levels did not vary between OGF and control groups. Mice receiving OGF by continuous infusion using minipumps, or by daily intratumoral injection, had characteristics of tumorigenicity similar to their corresponding control animals, although the OGF levels in mice receiving the OGF by minipump were elevated 18-fold greater than the control group. These data indicate that: i) the inhibitory action of OGF may be ubiquitous for SCCHN, ii) OGF treatment alters the characteristics of the OGF receptor but not of plasma OGF levels, and iii) the magnitude of effects of OGF on SCCHN is dependent on the route of administration.

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