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.
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 humanovarian 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 humanovarian cancer in a xenograft model, and provides novel non-toxic therapies for the treatment of this lethal neoplasia.
Authors: David P Stockdale; Michelle B Titunick; Jessica M Biegler; Jessie L Reed; Alyssa M Hartung; David F Wiemer; Patricia J McLaughlin; Jeffrey D Neighbors Journal: Bioorg Med Chem Date: 2017-06-27 Impact factor: 3.641
Authors: Silvia Zecchini; Lorenzo Bombardelli; Alessandra Decio; Marco Bianchi; Giovanni Mazzarol; Fabio Sanguineti; Giovanni Aletti; Luigi Maddaluno; Vladimir Berezin; Elisabeth Bock; Chiara Casadio; Giuseppe Viale; Nicoletta Colombo; Raffaella Giavazzi; Ugo Cavallaro Journal: EMBO Mol Med Date: 2011-07-08 Impact factor: 12.137
Authors: Giacomo Montagna; Hersh V Gupta; Margaret Hannum; Kay See Tan; Jasme Lee; Joseph R Scarpa; George Plitas; Takeshi Irie; Patrick J McCormick; Gregory W Fischer; Monica Morrow; Joshua S Mincer Journal: Br J Anaesth Date: 2020-11-19 Impact factor: 9.166