Anti-ovarian cancer effects of forsythiaside A: insights from in vitro and in vivo studies.

BACKGROUND: Ovarian cancer is a significant challenge due to its late-stage diagnosis and high mortality rates. The identification of new therapeutic agents is crucial. Forsythiaside A (FSA), derived from Forsythia suspensa, has demonstrated anti-cancer effects in other cancers, but its impact on ovarian cancer remains unexplored. This study was therefore undertaken to explore the potential anti-ovarian cancer activities of FSA and elucidate its underlying mechanisms in both in vitro and in vivo settings. METHODS: SK-OV-3 and OVCAR3 ovarian cancer cell lines were used for in vitro experiments. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, cell cycle distribution was analyzed by flow cytometry, and cell migration and invasion were evaluated through wound healing and Transwell assays. Apoptosis and necrosis were detected using YO-PRO-1 iodide/propidium iodide staining. Western blotting quantified the expression of key apoptosis-related proteins. Transcriptomic analysis was performed on FSA-treated SK-OV-3 cells. In vivo anti-tumor effects were examined in a subcutaneous SK-OV-3 xenograft model in nude mice. RESULTS: FSA significantly reduced the proliferation of both SK-OV-3 and OVCAR3 cells in a dose- and time-dependent manner. FSA induced G1 phase cell cycle arrest in both cell lines and inhibited their migration and invasion. It promoted cell death through increased apoptosis and necrosis, with Western blot showing upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Transcriptomic analysis revealed significant changes in gene expression, affecting pathways related to cell cycle control, apoptosis, and cancer progression. In vivo studies demonstrated that FSA suppressed SK-OV-3 xenograft tumor growth. CONCLUSIONS: FSA effectively inhibits ovarian cancer cell proliferation, migration, and invasion, and induces G1 arrest and apoptosis. These results highlight FSA as a promising natural compound for the development of new ovarian cancer treatments.