Anthraquinone derivative KA-4s inhibiting the proliferation and inducing ferroptosis of SKOV3/DDP cells

Objective:To investigate the effect of anthraquinone derivative KA-4s on the proliferation of human cisplatin-resistant ovarian cancer SKOV3/DDP cells in vitro and the mechanism of inducing ferroptosis. Methods:SKOV3/DDP cells were divided into control group and different concentrations (2 μmol/L, 5 μmol/L and 7 μmol/L) of anthraquinone derivative KA-4s groups. The effects of KA-4s and cisplatin (DDP) alone on the viability of SKOV3/DDP cells were determined by MTT assay, the migration ability of SKOV3/DDP cells was detected by scratch test, the mitochondrial morphological changes were detected by mitochondrial green fluorescent probe (Mito-Tracker Green), and the mitochondrial ultrastructure was observed by transmission electron microscopy. Ferroptosis inducer RSL3 was used as a positive control group, intracellular reactive oxygen species (ROS) levels were detected by DCFA-DA fluorescent probe, the total intracellular ferritin content was detected by colorimetry, and the expression of ferroptosis-related proteins GPX4 and FSP1 was detected by western blotting. Results:After treatment with KA-4s and DDP for 48 h, the proliferation of ovarian cancer SKOV3/DDP cells was significantly inhibited, and KA-4s had a stronger inhibitory effect than DDP (P＜0.001), and could inhibit cell migration. After KA-4s treatment, mitochondria were damaged, mitochondrial structure changed, membrane density increased, and ridge decreased or even disappeared. Compared with the blank control group, the intracellular ROS levels of the positive RSL3 group and KA-4s group were increased (all P＜0.001), the total iron content in 5 μmol/L KA-4s group was significantly increased (P＜0.001), and the expression of GPX4 and FSP1 proteins in ovarian cancer SKOV3/DDP cells was decreased (P＜0.01), but GPX4 expression in the normal ovarian IOSE80 cells was unchanged. Conclusion:KA-4s can inhibit the proliferation, migration and induce ferroptosis of SKOV3/DDP cells.