The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice.

Abstract

OBJECTIVE:

The opioid growth factor (OGF) and its receptor, OGFr, serve as a tonically active inhibitory axis regulating cell proliferation in normal cells and a variety of cancers, including human ovarian cancer. Blockade of OGF and OGFr with the nonselective opioid receptor antagonist naltrexone (NTX) upregulates expression of OGF and OGFr. Administration of a low dosage of NTX (LDN) blocks endogenous opioids from opioid receptors for a short period of time (4-6 h) each day, providing a window of 18-20 h for the upregulated opioids and receptors to interact. The present study investigated the repercussions of upregulating the OGF-OGFr axis by treatment with OGF or LDN on human ovarian tumorigenesis in vivo.

METHODS:

Female nude mice were transplanted intraperitoneally with SKOV-3 human ovarian cancer cells and treated on a daily basis with OGF (10 mg/kg), LDN (0.1 mg/kg), or an equivalent volume of vehicle (saline). Tumor burden, as well as DNA synthesis, apoptosis, and angiogenesis was assessed in tumor tissue following 40 days of treatment.

RESULTS:

OGF and LDN markedly reduced ovarian tumor burden (tumor nodule number and weight). The mechanism of action was targeted to an inhibition of tumor cell proliferation and angiogenesis; no changes in cell survival were noted.

CONCLUSIONS:

This study shows that a native opioid pathway can suppress human ovarian cancer in a xenograft model, and provides novel non-toxic therapies for the treatment of this lethal neoplasia.

• Authors: Renee N Donahue, Patricia J McLaughlin, Ian S Zagon
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 122 Issue 2 Pg. 382-8 (Aug 2011) ISSN: 1095-6859 [Electronic] United States
• PMID: 21531450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Narcotic Antagonists
• Receptors, Opioid
• methionine-enkephalin receptor
• Enkephalin, Methionine
• Naltrexone
• DNA

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• DNA (biosynthesis)
• Disease Progression
• Enkephalin, Methionine (analysis, therapeutic use)
• Female
• Humans
• Mice
• Mice, Nude
• Naltrexone (therapeutic use)
• Narcotic Antagonists (therapeutic use)
• Neovascularization, Pathologic (prevention & control)
• Ovarian Neoplasms (blood supply, pathology)
• Receptors, Opioid (analysis, physiology)
• Xenograft Model Antitumor Assays