Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel

Stefan Buchholz, Andrew V. Schally, Jörg B. Engel, Florian Hohla, Elmar Heinrich, Frank Koester, Jozsef L. Varga, Gabor Halmos

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various cancers. In this study, we investigated the effectiveness of treatment with GHRH antagonist JMR-132 alone and in combination with docetaxel chemotherapy in nude mice bearing MX-1 human breast cancers. Specific high-affinity binding sites for GHRH were found on MX-1 tumor membranes using ligand competition assays with 125I-labeled GHRH antagonist JV-1-42. JMR-132 displaced radiolabeled JV-1-42 with an IC50 of 0.14 nM, indicating a high affinity of JMR-132 to GHRH receptors. Treatment of nude mice bearing xenografts of MX-1 with JMR-132 at 10 μg per day s.c. for 22 days significantly (P < 0.05) inhibited tumor volume by 62.9% and tumor weight by 47.8%. Docetaxel given twice at a dose of 20 mg/kg i.p. significantly reduced tumor volume and weight by 74.1% and 58.6%, respectively. Combination treatment with JMR-132 (10 μg/day) and docetaxel (20 mg/kg i.p.) led to growth arrest of most tumors as shown by an inhibition of tumor volume and weight by 97.7% and 95.6%, respectively (P < 0.001). Because no vital cancer cells were detected in some of the excised tumors, a total regression of the tumors was achieved in some cases. Treatment with JMR-132 also strongly reduced the concentration of EGF receptors in MX-1 tumors. Our results demonstrate that GHRH antagonists might provide a therapy for breast cancer and could be combined with docetaxel chemotherapy to enhance the efficacy of treatment.

Original languageEnglish (US)
Pages (from-to)1943-1946
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number6
DOIs
StatePublished - Feb 6 2007

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Keywords

  • Breast cancer
  • Cancer therapy
  • Chemotherapeutic agents
  • Growth hormone-releasing hormone receptors

ASJC Scopus subject areas

  • Genetics
  • General

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