Effect and mechanism of Erastin on ferroptosis of acute myeloid leukemia cells
10.19405/j.cnki.issn1000-1492.2025.01.003
- Author:
Xiandong Jiang
1
,
2
;
Yingying Huang
1
,
2
;
Xiaoying Hong
1
,
2
;
Xindi Lin
3
;
Donghong Lin
1
,
2
;
Liping Lin
1
,
2
Author Information
1. School of Medical Technology and Engineering，Fujian Medical University，Fuzhou 350122
2. Key Laboratory of Clinical Laboratory Technology for Precision Medicine，Fujian Province University，Fuzhou 350122
3. Reproductive Medicine Center of Fujian Maternal and Child Health Hospital，Fuzhou 350003
- Publication Type:Journal Article
- Keywords:
Erastin;
LPCAT3;
ferroptosis;
UPR classic pathway;
acute myeloid leukemia;
4-phenylbutyric acid;
mechanism of action
- From:
Acta Universitatis Medicinalis Anhui
2025;60(1):15-21
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms.
Methods :Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed.
Results :Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state.
Conclusion :Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.
- Full text:2025030416073533763爱拉斯汀对急性髓系白血病细...死亡的影响及其相关作用机制_江贤栋.pdf
