부산대학교 도서관

Ovarian cancer (OC) is a refractory cancer that shows recurrence due to the acquisition of resistance to anticancer drugs, including cisplatin. However, the molecular mechanism underlying the acquisition of cisplatin resistance by cancer cells remains largely unknown. In the present study, two sets of ovarian endometrioid carcinoma cell lines were used: The parental A2780 cell line, the OVK18 cell line, and their derived cisplatin-resistant cells. It was found that cisplatin could induce ferroptosis in these parental cells by enhancing mitochondrial membrane potential and lipid peroxidation as assessed by flow cytometric analysis, and that expression of Ferredoxinl (Fdxl), an iron-sulfur protein localized to the mitochondria, could be upregulated in cisplatin-resistant cells in the absence of cisplatin. Intriguingly, it was shown that the siRNA-mediated depletion of Fdxl in cisplatin-resistant cells resulted in enhanced ferroptosis by increasing the mitochondrial membrane potential and lipid peroxidation induced by cisplatin. By examining Fdxl expression with immunohistochemical analysis in clinical specimens from patients with OC, higher expression of Fdxl was detected in cisplatin-resistant specimens than in cisplatin-sensitive specimens. Collectively, these results indicated that Fdxl may be a novel and suitable diagnostic/prognostic marker and therapeutic molecular target for the treatment of cisplatin-resistant OC. Key words: ovarian cancer, cisplatin resistance, Ferredoxin1, ferroptosis, mitochondria
Introduction Ovarian cancer (OC) has highmorbidity and mortality rates, and age-standardized mortality is the highest among gynecological cancers worldwide (1). As patients are often asymptomatic, >40% of cases are advanced [...]