Beclin1-SLC7A11 Complex Regulates K562/ADM Cells Ferroptosis And Its Effect On Multidrug Resistance Of Cells

Background and purpose:Acute leukemia is the most common cancer in children,and tumor multidrug resistance is the main problem in current treatment.Ferroptosis is a new death mode of cancer cells.Ferroptosis can reverse the drug resistance of tumor cells to chemotherapeutic drugs.Beclin1-SLC7A11 complex can inhibit ferroptosis induced by SLC7A11 activity.This project intends to use K562/ADM leukemia cells as the main research object to explore the molecular mechanism that Beclin1-SLC7A11 may be involved in the regulation of iron death and drug resistance in K562/ADM leukemia cells.To provide experimental support for finding new treatment methods for leukemia.Methods:1.K562 / ADM cells were treated with different concentrations of Erastin.48 hours later,the cell survival rate and 50% death concentration were detected by CCK-8 assay,and the intracellular propanediol level was detected by ELISA kit for Malondialdehyde.2.K562/ADM cells were treated with different concentrations of Erastin.48 hours later,the expression levels of SLC7A11 and P-gp proteins were detected by Western Blot.3.K562/ADM cells were treated with Erastin and doxorubicin.48 hours later,CCK-8 assay was used to detect the viability of K562/ADM cells.Results:1.Erastin inhibited the proliferation of K562/ADM cells in a dosedependent manner.With the increase of Erastin concentration,the survival rate of K562/ADM cells decreased gradually.After being treated with 40,80 and 160 μ mol / L Erastin for 48 hours,the cell survival rates were52.31%,25.98%,8.89%,respectively,and the IC50 concentration was42.44μmol/ L.2.After K562/ADM cells were treated with 0、20、40、60、80、160μ mol /L Erastin for 48 h,the intracellular MDA content was 30.44、43.54、60.47、73.54、75.05 and 76.07ng/m L,respectively.3.Compared with the control group,the combination therapy could increase the sensitivity of K562 / ADM cells to doxorubicin.4.Compared with the blank control group,the expression of P-gp in K562/ADM cells in 160 μmol/ L Erastin group had no significant change,but the expression of SLC7A11 decreased significantly.Conclusion:1.Erastin can induce ferroptosis in K562/ADM cells,and its mechanism may be related to the formation of Beclin1-SLC7A11 complex.2.The sensitivity of K562/ADM cells to doxorubicin was increased by ferroptosis induced by erastin,but had nothing to do with P-gp.