Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation
Cisplatin-based chemotherapy often results in ovarian cancer (OC) chemical resistance and treatment failure. The combination of natural compounds with platinum-based agents is a new strategy for overcoming cisplatin resistance. At present, the synergistic effects and mechanism of combination of shikonin and cisplatin to overcome cisplatin resistance in OC are still unknown. This study was to evaluate the synergistic effects of shikonin and cisplatin on cisplatin-resistant OC cells and to assess the underlying molecular basis for these effects. Cell counting kit-8 assay, colony-formation assay, proteomic analysis, reactive oxygen species (ROS) detection, lipid peroxidation (LPO) detection, Fe In vitro, shikonin and cisplatin were shown to synergistically reduce the viability of cisplatin-resistant OC cells. Proteomic results demonstrated that the combination of the two drugs induced a ferroptotic process, as evidenced by increased levels of ROS, LPO, and Fe We report for the first time that the co-treatment of shikonin and cisplatin overcomes cisplatin resistance in OC through ferroptosis. Mechanistic analysis reveals the co-treatment induces ferroptosis through upregulation of HMOX1 that promotes Fe
