Effect of UVRAG Gene on Ferroptosis Induced by Sorafenib in K562 Cells
10.19746/j.cnki.issn1009-2137.2024.03.001
- VernacularTitle:UVRAG基因在索拉非尼诱导的K562细胞铁死亡中的作用
- Author:
Yan-Min MA
1
;
Yan WANG
;
Min YANG
;
Ze-Min CAI
;
Xiao-Cheng YIN
Author Information
1. 南华大学衡阳医学院附属第一医院儿科,湖南衡阳 421000
- Keywords:
ferroptosis;
sorafenib;
UV radiation resistance-associated gene;
leukemia
- From:
Journal of Experimental Hematology
2024;32(3):653-657
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of UV radiation resistance-associated gene(UVRAG)on ferroptosis induced by sorafenib in leukemia K562 cells.Methods:K562 cells were treated with 0,0.625,1.25,2.5,5,10,and 20μmol/L sorafenib for 24 or 48 hours,and the cell viability was detected by CCK-8 assay.Flow cytometry technology was used to detect the changes of reactive oxygen species(ROS)in K562 cells treated with 0,5,and 10 μmol/L sorafenib for 24 hours.Western blot was used to detect the protein expression of GPX4 in K562 cells treated with 0,5,and 10μmol/L sorafenib and pretreatment with ferroptosis inhibitor.A recombinant lentiviral vector was used to construct UVRAG overexpression cell line in K562 cells.qPCR and Western blot were used to verify UVRAG gene overexpression,and Western blot detected the effect of UVRAG on the protein expression of GPX4 and HMGB1 after treatment with sorafenib.Results:Different concentrations of sorafenib could significantly inhibit the proliferation of K562 cells,and the cell viability gradually decreased with the increase of concentration(r24h=-0.9841,r48 h=-0.9970).The level of ROS was increased(When the concentration was 10 μmol/L,P＜0.00 1),while the expression of GPX4 protein was decreased in the process of 0,5,10 μmol/L sorafenib-induced K562 cell death(P＜0.05),and the decrease in GPX4 protein could be partially reversed by pretreatment with ferroptosis inhibitor(P＜0.05).Compared with NC group and NC-Sorafenib group,the expression of GPX4 protein was significantly decreased(both P＜0.05),while HMGB1 protein was significantly increased(both P＜0.05).Conclusion:Sorafenib can induce ferroptosis in K562 cells,and this process can be promoted by UVRAG.
