Combination of GHRH antagonists and docetaxel shows experimental effectiveness for the treatment of triple-negative breast cancers

In preclinical studies, antagonists of growth hormone-releasing hormone (GHRH) have demonstrated inhibitory effects on the growth of various types of cancers expressing the pituitary type of GHRH receptors (pGHRH-R) and/or its active splice variant 1 (SV1). In this study, we investigated the effectiveness of the treatment of MDA-MB-231 human triple-negative breast cancer (TNBC) with GHRH antagonist JMR-132 alone or in combination with docetaxel. Receptor expression in the MDA-MB-231 human breast cancer cell line was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Cell viability assays were performed on MDA-MB-231 cells treated with JMR-132, docetaxel or in combination. For studies in vivo, a subcutaneous nude mouse xenograft model was used. JMR-132 was administered s.c. at a dose of 10 µg/day and docetaxel at a dose of 10 mg/kg i.p. given on day 1 and 5. Similar regimens were used for the combination of both substances. At the end of the experiment, an mRNA-based human cancer pathway array including 84 major genes was performed on the tumor tissue of mice treated with JMR-132 to elucidate the mechanism of action of GHRH antagonists in vivo. The in vitro proliferation studies revealed that JMR-132 and docetaxel decreased the cell viability in a dose-dependent manner. The combination of both treatments produced a significantly greater inhibition of cell viability compared to the single agents. Treatment of nude mice bearing MDA-MB-231 xenografts with JMR-132 and docetaxel significantly (p