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Updated: Jun 2, 2026
Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing
Published on: September 15, 2023
The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice
Renee N Donahue1, Patricia J McLaughlin, Ian S Zagon
1Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA.
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.
Insights
The opioid growth factor (OGF) pathway, when upregulated by OGF or low-dose naltrexone (LDN), significantly reduced human ovarian cancer burden in mice. This novel, non-toxic approach targets tumor cell proliferation and angiogenesis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The opioid growth factor (OGF) and its receptor (OGFr) form an inhibitory axis controlling cell proliferation in normal tissues and cancers.
- Naltrexone (NTX), a nonselective opioid receptor antagonist, upregulates OGF and OGFr expression.
- Low-dose naltrexone (LDN) administration creates a daily window for upregulated OGF-OGFr axis interaction.
Purpose of the Study:
- To investigate the effects of upregulating the OGF-OGFr axis via OGF or LDN treatment on human ovarian cancer growth in vivo.
- To assess the impact of these treatments on tumor burden, DNA synthesis, apoptosis, and angiogenesis.
Main Methods:
- Human ovarian cancer cells (SKOV-3) were xenografted into female nude mice.
- Mice received daily intraperitoneal injections of OGF (10 mg/kg), LDN (0.1 mg/kg), or vehicle (saline) for 40 days.
- Tumor burden, DNA synthesis, apoptosis, and angiogenesis were evaluated in tumor tissues.
Main Results:
- Both OGF and LDN treatments significantly reduced ovarian tumor burden, including nodule number and weight.
- The observed antitumor effects were attributed to the inhibition of tumor cell proliferation and angiogenesis.
- No significant changes in tumor cell survival (apoptosis) were detected.
Conclusions:
- Upregulation of the native OGF-OGFr opioid pathway effectively suppresses human ovarian cancer in a xenograft model.
- OGF and LDN represent novel, non-toxic therapeutic strategies for treating ovarian cancer.
- This study highlights the potential of targeting endogenous opioid pathways for cancer therapy.
