BACKGROUND:Salvianolic acid F (SAF), an important water-soluble monomeric component, is derived from the herbal medicine Salvia miltiorrhiza (SM) Bunge. Although SAF has been suggested to suppress various cancers, its role in ovarian cancer (OC) and the underlying mechanisms remain largely unclear.
OBJECTIVES:This study aimed to investigate the effects of SAF on OC cell growth, invasion, migration, and apoptosis, as well as to elucidate the underlying mechanisms, including those involving the EP300/PI3K/AKT signaling pathway.
MATERIAL AND METHODS:In vitro cell culture experiments were conducted to assess the effects of SAF on the proliferation, migration, invasion, and apoptosis of OVCAR-3 (Ovarian Cancer Cell Line 3) and SK-OV-3 (Sloan-Kettering Ovarian Cancer 3) cells. Network pharmacology was further employed to explore SAF's impact on OC and to elucidate the potential underlying mechanisms. The EP300-mediated PI3K/AKT signaling pathway was selected for validation to confirm SAF's effects on inducing apoptosis and inhibiting cell proliferation in these OC cell lines.
RESULTS:Salvianolic acid F suppressed the growth, invasion and migration of SK-OV-3 and OVCAR-3 cells, and induced apoptosis. A network pharmacology analysis of SAF's effects on OC identified core targets, TP53, EP300, STAT3, MMP9, NFKB1, HIF1A, and PTGS2, through protein-protein interaction (PPI) network analysis using the STRING database. Salvianolic acid F inhibited EP300 expression in SK-OV-3 cells, reduced the p-PI3K/PI3K ratio, and increased both the Bax/Bcl-2 ratio and the cleaved caspase-3/caspase-3 ratio in OVCAR-3 and SK-OV-3 cells. However, the addition of A485, an EP300 inhibitor, did not further enhance the effects of SAF.
CONCLUSIONS:Salvianolic acid F inhibited OC cell growth, migration and invasion while promoting apoptosis. The EP300/PI3K/AKT pathway is a key mechanism through which SAF regulates OC progression. Additionally, SAF may represent a promising candidate drug for treating OC.
