Study on the death mode of ovarian cancer cells induced by anthraquinone modifier 4X through triggering endoplasmic reticulum stress

Objective:To investigate the death mode and mechanism of ovarian cancer cell SKOV3 and cisplatin-resistant ovarian cancer cell SKOV3/DDP induced by anthraquinone modifier 4X.Methods:SKOV3 and SKOV3/DDP cells were divided into control group and different concentrations(2 μmol/L, 4 μmol/L and 8 μmol/L) of anthraquinone modifier 4X group, respectively.The cell proliferation rate was detected by MTT assay, the cell morphology was observed by hematoxylin-eosin (HE) staining, the mitochondrial morphology was observed by mito-trayer-green fluorescence probe, and the cell ultrastructure was observed by transmission electron microscopy.The expressions of endoplasmic reticulum stress-related proteins (GRP78, PERK), apoptosis protein(CHOP)and ferroptosis key protein(GPX4)were detected by western blotting.Apoptosis inhibitor Z-VAD-FMK was added and co-treated with anthraquinone modifier 4X, and the apoptosis rate of cells was detected by flow cytometry.Results:After treatment with anthraquinone modifier 4X for 48 hours, the proliferation of SKOV3 and SKOV3/DDP cells was significantly inhibited (P< 0.05).After treatment with anthraquinone modifier 4X, there were obvious vacuoles in the cytoplasm of SKOV3 and SKOV3/DDP, and some vacuoles involved the nucleus.Mitochondrial damage was observed in both SKOV3 and SKOV3/DDP.After treatment with anthraquinone modifier 4X, the mitochondria of the cells were shrunk, the membrane density increased, and the ridge disappeared.Compared with the control group, the apoptosis rate of SKOV3 and SKOV3/DDP cells in the anthraquinone modifier 4X group increased (P< 0.05), and the promoting effect of anthraquinone modifier 4X on cell apoptosis was inhibited by adding Z-VAD-FMK(P< 0.05).Anthraquinone modifier 4X could upregulate the expressions of GRP78, PERK, ATF4 and CHOP in SKOV3 and SKOV3/DDP cells, and downregulate the expression of GPX4 to varying degrees(all P< 0.05).Conclusion:Anthraquinone modifier 4X May induce endoplasmic reticulum stress and the apoptosis and ferroptosis in SKOV3 and SKOV3/DDP cells, thus playing an anti-ovarian cancer role.