GHRH Antagonist Halts Ovarian Cancer Cell Growth via EGFR-Akt Pathway

Ovarian cancer remains a highly lethal gynecological malignancy, often diagnosed at advanced stages with poor prognosis. Current treatments face challenges like drug resistance and significant side effects. Research suggests that growth hormone-releasing hormone (GHRH) and its receptors are often overexpressed in various cancers, including ovarian cancer, promoting tumor growth and survival. However, the precise mechanisms by which GHRH antagonists exert their anti-cancer effects in ovarian cancer, particularly concerning specific signaling pathways, are not fully understood. This study aimed to elucidate how GHRH antagonists inhibit ovarian cancer cell proliferation and the underlying molecular pathways involved.

Treatment with the GHRH antagonist MIA-602 significantly inhibited the proliferation of both SKOV-3 and OVCAR-3 ovarian cancer cells in a dose- and time-dependent manner. At a concentration of 1 µM, MIA-602 reduced cell viability by approximately 45% after 48 hours compared to untreated controls (p<0.01). Furthermore, the antagonist induced apoptosis, leading to a 2.3-fold increase in apoptotic cells at 1 µM after 72 hours (p<0.005). This effect was specific, as total EGFR and Akt protein levels remained largely unchanged. The most significant finding was that MIA-602 treatment led to a marked downregulation of phosphorylated EGFR and Akt levels, with a 60% reduction in p-EGFR and a 55% reduction in p-Akt at 1 µM (p<0.01), indicating a direct impact on this critical pro-survival pathway.