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

Gynecol Oncol. 2011 Aug;122(2):382-8. doi: 10.1016/j.ygyno.2011.04.009. Epub 2011 Apr 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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