Modulation of the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: novel therapies for squamous cell carcinoma of the head and neck

Head Neck. 2012 Apr;34(4):513-9. doi: 10.1002/hed.21759. Epub 2011 May 16.

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.

Publication types

  • Comparative Study

MeSH terms

  • Aminoquinolines / administration & dosage*
  • Analysis of Variance
  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • DNA / biosynthesis
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Imiquimod
  • Injections, Intraperitoneal
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / genetics
  • Reference Values
  • Squamous Cell Carcinoma of Head and Neck
  • Transplantation, Heterologous
  • Treatment Outcome
  • Tumor Burden
  • Up-Regulation

Substances

  • Aminoquinolines
  • Receptors, Opioid
  • methionine-enkephalin receptor
  • DNA
  • Imiquimod