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Modulation of the opioid growth factor ([Met5]-enkephalin)–opioid growth factor receptor axis: Novel therapies for squamous cell carcinoma of the head and neck

Authors

  • Patricia J. McLaughlin MS, DEd,

    Corresponding author
    1. Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
    • Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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  • Jaimon K. Stucki BS,

    1. Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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  • Ian S. Zagon MS, PhD

    1. Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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Abstract

Background

The opioid growth factor (OGF)–OGF receptor (OGFr) axis is a constitutively expressed biologic pathway regulating cell proliferation of squamous cell carcinoma of the head and neck (SCCHN). This study investigated modulation of the OGF–OGFr system by (1) exogenous OGF, (2) upregulation of OGFr using imiquimod, or (3) intermittent opioid receptor blockade with a low dose of naltrexone on progression of established SCCHN.

Methods

Nude mice with visible human SCCHN SCC-1 tumors received (1) OGF or low-dose naltrexone either 1, 3, or 7 times/week or (2) imiquimod 1 or 3 times/week. Tumor growth and DNA synthesis were monitored.

Results

OGF and low-dose naltrexone increased the latency from visible to measurable tumors up to 1.6-fold. OGF, low-dose naltrexone, and imiquimod treatment markedly reduced tumor volume and weight, and decreased DNA synthesis in tumors.

Conclusions

Modulation of the native OGF–OGFr regulatory network in SCCHN represents a novel nontoxic and highly efficacious approach for treatment of SCCHN. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

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