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

Renee N. Donahue, Patricia McLaughlin, Ian Zagon

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)382-388
Number of pages7
JournalGynecologic Oncology
Volume122
Issue number2
DOIs
StatePublished - Aug 1 2011

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Naltrexone
Ovarian Neoplasms
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Opioid Receptors
Neoplasms
Tumor Burden
Cell Proliferation
Narcotic Antagonists
Heterografts
Nude Mice
Cell Survival
Carcinogenesis
Up-Regulation
Apoptosis
Weights and Measures
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

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title = "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.",
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The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. / Donahue, Renee N.; McLaughlin, Patricia; Zagon, Ian.

In: Gynecologic Oncology, Vol. 122, No. 2, 01.08.2011, p. 382-388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice

AU - Donahue, Renee N.

AU - McLaughlin, Patricia

AU - Zagon, Ian

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N2 - 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.

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