Induction of itraconazole on ferroptosis in triple-negative breast cancer cells and its possible mechanism
Objective To investigate the induction of itraconazole on ferroptosis in triple-negative breast cancer(TNBC)cells and its possible mechanism.Methods(1)MDA-MB-231 cell and BT-549 cell were assigned to control group or drug with different concentrations groups,respectively,and complete medium and itraconazole with different concentrations(2 µmol/L,4 µmol/L,8 µmol/L,16 µmol/L,32 µmol/L)were added for a 48-hour treatment,respectively,after then the CCK-8 method was used to detect cellular activity,and half inhibitory concentration(IC50)of itraconazole was calculated.(2)MDA-MB-231 cell and BT-549 cell were assigned to control group(adding complete medium),itraconazole group(adding itraconazole of 5 µmol/L),itraconazole+ferroptosis inhibitor group(adding itraconazole and Ferrostatin-1 of 5 µmol/L,respectively),or ferroptosis inhibitor group(adding Ferrostatin-1 of 5 µmol/L).The levels of lipid peroxide and glutathione of the two cells in the control group and the itraconazole group,cellular activity of the four groups,and protein expressions of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were detected.Results(1)The activities of MDA-MB-231 and BT-549 cells decreased with the increase of itraconazole concentration.IC50 of itraconazole on MDA-MB-231 and BT-549 cells was 4.648 µmol/L and 4.612 µmol/L,respectively.(2)Glutathione level of MDA-MB-231 cell and BT-549 cell in the itraconazole group was decreased as compared with the control group,whereas lipid peroxide level was elevated as compared with the control group(P<0.05).(3)Compared with the control group,the activities of MDA-MB-231 and BT-549 cells,and protein expressions of SLC7A11 and GPX4 in the itraconazole group were decreased(P<0.05).Compared with the itraconazole group,the activities of MDA-MB-231 and BT-549 cells,and protein expressions of SLC7A11 and GPX4 in the itraconazole+ferroptosis inhibitor group were elevated(P<0.05).Conclusion Itraconazole may induce cellular ferroptosis by regulating SLC7A11/GPX4 axis,thereby inhibiting the proliferation of TNBC cells.
Triple-negative breast cancerItraconazoleFerroptosisCell proliferationSolute carrier family 7 member 11Glutathione peroxidase 4Mechanism
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