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 vitroand the mechanism of inducing ferroptosis.Meth-ods: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 via-bility of SKOV3/DDP cells were determined by MTT assay,the migration ability of SKOV3/DDP cells was de-tected 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 micros-copy.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 blot-ting.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 in-hibit cell migration.After KA-4s treatment,mitochondria were damaged,mitochondrial structure changed,mem-brane density increased,and ridge decreased or even disappeared.Compared with the blank control group,the in-tracellular 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 ovari-an IOSE80 cells was unchanged.Conclusion:KA-4s can inhibit the proliferation,migration and induce ferropto-sis of SKOV3/DDP cells.
anthraquinone derivativeSKOV3/DDP cellsferroptosisglutathione peroxidase 4reactive oxygen species
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