Endocrine Abstracts

Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers. In this study, we investigated the effectiveness of GHRH antagonist JMR-132 treatment in ovarian cancer cell lines (SKOV-3, CaOV-3 and OVCAR-3). Using MTT assay, we found that JMR-132 has a strong anti-proliferation effects on SKOV-3 and CaOV-3 cells in a time (0, 24 h, 48 h, 72 h, 96 h) and dose (0, 25 nM, 50 nM, 100 nM and 200 nM) dependent manner. Also, JMR132-induced the activation and increases cleaved caspase-3 in a time-dependent manner in both cell lines. In addition, flow cytometry assay showed that there is a G1 phase cell circle arrest after treatment of JMR-132 in these two cell lines. With 100 nM JMR-132 per day for 4 days, the phosphorylation of Akt (p-Akt) decreased significantly, suggesting that JMR-132 inhibit the PI3K-AKT pathways in ovarian cancer cells. Treatment of the SKOV-3 and CaOV-3 cell with specific PI3K inhibitor LY294002 (10 nM) in combination with the presence or absence of EGF (10 ug/ml) abolished JMR-132 attenuated EGF-induced proliferation in both cell lines. More importantly, continuous treatment with JMR-132 reduced the expression of total EGF receptor (EGFR) in a time dependent manner. Knockdown of the endogenous expression of EGFR by siRNA attenuated JMR-132 inhibited proliferation of SKOV-3 and CaOV-3 cells by EGF. In summary, the present study demonstrates that the antiproliferation effect exerted by GHRH antagonist JMR-132 is due in part by interference of the EGF receptor-Akt pathway in ovarian cancer cell.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.