Abstract 697: Inhibition of Cancer Progression by Upregulation of the Opioid Growth Factor (OGF) - OGF Receptor (OGFr) Axis Using Imquimod or Low Dose Naltrexone

Opioid growth factor (OGF, [Met5] enkephalin), is a tonically active, negative growth factor, and interacts with a nuclear-associated receptor, OGFr. The OGF-OGFr axis mediates cell proliferation by targeting cyclin-dependent kinase inhibitory pathways. Overexpression of OGFr by pharmacological modulation of several human cancer cell lines in tissue culture has been shown to result in decreased cell replication in response to either elevated endogenous OGF or exogenous administration of this inhibitory peptide. The present study examines tumor progression in nude mice whereby established tumors of human squamous cell carcinoma of the head and neck are treated by 2 methods of upregulation of the OGF-OGFr axis: imiquimod or low dosages of the opioid antagonist naltrexone (LDN; 0.1 mg/kg naltrexone). Tumor volume was monitored 3 times weekly. Some tumors were assessed for immunohistochemical levels of OGF and OGFr. Imiquimod, a promoter of OGFr gene activity, was administered topically either 1X or 3X each week. LDN was given systemically 1X or 3X per week, or daily. At the time of death, tumor volumes for the 1X and 3X imiquimod treated mice were 18 and 47%, respectively, smaller than controls, and tumor weights were decreased 36 and 43%, respectively relative to controls. All LDN treatment regimens effectively reduced tumor volume relative to mice receiving vehicle, with a regimen-related decrease in tumor growth noted throughout the study. At termination on day 35, mean tumor volumes of mice exposed to LDN were reduced from vehicle-treated controls by 35%, 61% and 84% when given 1X/week (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 697.