Assessing Auranofin for Second-Line Use in Chemoresistant Ovarian Cancer: Effects on Tumour Spheroid and Primary Cell Growth

: Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women and the most lethal gynaecological malignancy. The high mortality rate is primarily due to late diagnosis and the lack of targeted therapies. The gold standard treatment consists of debulking surgery followed by platinum/taxane-based chemotherapy, which is initially effective in approximately 75% of patients. However, most women experience relapse and develop chemoresistance. To date, no therapy has proven to be decisive, underscoring the need for research into second-line or alternative treatments to overcome chemoresistance and prevent relapses. Auranofin (AF) is a promising repositioned anticancer agent with a multifaceted mode of action both cancer cell type- and dose-dependent. The current study evaluated AF's cytotoxicity on multicellular tumour spheroids derived from three ovarian cancer cell lines (SKOV3, A2780, and A2780 cisplatin-resistant). Results demonstrated that AF inhibited spheroid formation and growth by inducing apoptosis. Furthermore, we showed that AF's mode of action involves the PI3K/Akt and NF-κB pathways, and we highlighted differences in drug responses between cisplatin-sensitive, resistant, and primary ovarian cancer cells. Finally, by examining the efficacy of AF and cisplatin in combination, we identified differential sensitivities among the cell lines and primary ovarian cancer cells.