安徽医科大学学报2025，Vol.60Issue(1)：15-21,7.DOI:10.19405/j.cnki.issn1000-1492.2025.01.003
爱拉斯汀对急性髓系白血病细胞铁死亡的影响及其相关作用机制
Effect and mechanism of Erastin on ferroptosis of acute myeloid leukemia cells
摘要
Abstract
Objective To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3)in Erastin-in-duced ferroptosis of acute myeloid leukemia(AML)cells and its related molecular regulatory mechanisms.Meth-ods Tetrazolium salt(MTS)method was used to detect the sensitivity of different AML cells to the classic ferrop-tosis inducer Erastin,real time quantitative polymerase chain reaction(qPCR)was used to detect the basal expres-sion level of LPCAT3 mRNA,and the correlation between them was analyzed.Lentivirus-mediated LPCAT3 overex-pression AML cell lines(OE group)and negative control lines(NC group)were constructed.After Erastin inter-vention,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 IC50 of the four types of AML cells to Erastin was negatively correlated with the expression level of LPCAT3(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 clas-sic pathway molecules PERK,ATF4,and GRP78 mRNA 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 of LPCAT3 can promote ferroptosis in K562 cells,and this process is negatively regulated by the classical UPR pathway PERK/ATF.关键词
爱拉斯汀/溶血磷脂酰胆碱酰基转移酶3/铁死亡/UPR经典通路/急性髓系白血病/4-苯基丁酸/作用机制Key words
Erastin/LPCAT3/ferroptosis/UPR classic pathway/acute myeloid leukemia/4-phenylbutyric acid/mechanism of action分类
医药卫生引用本文复制引用
江贤栋,黄莹莹,洪小颖,林昕迪,林东红,林梨平..爱拉斯汀对急性髓系白血病细胞铁死亡的影响及其相关作用机制[J].安徽医科大学学报,2025,60(1):15-21,7.基金项目
福建省自然科学基金面上项目(编号:2021J01815) （编号:2021J01815）
国家自然科学基金面上项目(编号:82072355) Natural Science Foundation of Fujian Province(No.2021J01815) （编号:82072355）
National Natural Science Foundation of China(No.82072355) （No.82072355）
