Combination of antagonists of growth hormone-releasing hormone antagonist (GHRH) with rapamycin as a potential therapy in human breast cancers.

Abstract

e13627 Background: Antagonists of growth hormone releasing hormone (GHRH) are being developed fort he treatment of various cancers. In this study we investigated the effectiveness of treatment with GHRH Antagonist JMR 132 alone and in combination with rapamycin in hormonereceptor negative breast cancers in vitro and in vivo. Rapamycin represents an mTor Inhibitor. Methods: In the cell lines MDA MB 231 and SKBR 3 we evaluated the receptor status by Western Blot (GHRH-R, EGFR/Her1, Her2/neu) and immunohistochemistry (GHRH-R, ER, PgR). In our on vitro trials we investigated effect of JMR 132 and/or rapamycin on the cell cycle (G0, G1, S-Phase) by Flowcytometry. For animal experiments nude mice bearing MDA MB 231 human breast cancer xenografts subcutaneously where randomized to 4 treatment groups receiving 1. solvent (Control) 2. JMR-132 10 μg/d s.c 3. rapamycin 0,75 mg 2qw ip, 4 combination. Results: In the animal trials a significant inhibition of tumor growth was seen in the JMR 132 and rapamycin group compared to control. This effect was enhanced by the combination compared to all other treatment groups. A dose dependent inhibition of growth of the single agents and an additive effect of the combination was seen in the in vitro experiments. Conclusions: Our results show that JMR 132 is a potential partner for combined treatment strategies in breast cancer patients. No significant financial relationships to disclose.