山西医科大学学报2025，Vol.56Issue(4)：347-355,9.DOI:10.13753/j.issn.1007-6611.2025.04.002
ABCA1对肝癌细胞索拉非尼耐药的影响及其机制
Effect of ABCA1 on Sorafenib resistance in hepatocellular carcinoma cells and its mechanism
摘要
Abstract
Objective To investigate the effect of ATP-binding cassette transporter A1(ABCA1)on Sorafenib resistance in hepatocel-lular carcinoma cells and its underlying mechanism.Methods HepG2 cells were divided into three groups:HepG2 group,HepG2+si-NC group(transfected with negative control small interfering RNA),and HepG2+si-ABCA1 group(transfected with si-ABCA1).Sorafenib-resistant HepG2(HepG2/SR)cells were divided into three groups:HepG2/SR group,HepG2/SR+Vector group(transfected with pcDNA3.1 plasmid),and HepG2/SR+ABCA1 group(transfected with pcDNA3.1-ABCA1 plasmid).The mRNA expression of ABCA1 in HepG2 and HepG2/SR cells was detected by real-time quantitative PCR.Protein levels of ABCA1 and ferroptosis-related markers,solute carrier family 7 member 11(SLC7A11)and GPX4,were measured by Western blot.Cell viability was assessed using CCK-8 assays.Colony formation ability was evaluated in HepG2/SR cells by colony formation assay.Intracellular Fe2+level and reac-tive oxygen species(ROS)level were detected in HepG2 and HepG2/SR cells using FerroOrange staining and DCFH-DA probes,re-spectively.The cells in HepG2/SR+Vector group and HepG2/SR+ABCA1 group were treated with the protein synthesis inhibitor cyclo-heximide(CHX)for 0,1,2,4 h,and then the SLC7A11 degradation was detected.HepG2/SR cells were divided into HepG2/SR+ABCA1+Vector group and HepG2/SR+ABCA1+SLC7A11 group,and then protein expressions of SLC7A11 and GPX4,cell viability,colony formation ability,Fe²⁺ ion level,and ROS level were detected.Results Compared with HepG2 cells,ABCA1 mRNA and protein levels were significantly decreased in HepG2/SR cells(P<0.01).Cell viability was significantly increased in HepG2+si-ABCA1 group compared to HepG2+si-NC group(P<0.01).In HepG2/SR cells,ABCA1 overexpression significantly decreased cell viability and colony formation ability(P<0.01),downregulated SLC7A11 and GPX4 protein levels(P<0.05),and elevated Fe2+and ROS levels(P<0.05).With the increase of CHX treatment duration,SLC7A11 protein expression was gradually decreased in HepG2/SR+ABCA1 group,however there was no significant change of SLC7A11 protein expression in HepG2/SR+Vector group.Compared with HepG2/SR+ABCA1+Vector group,ROS and cellular ferrous iron levels were decreased in HepG2/SR+ABCA1+SLC7A11 group(P<0.05),and GPX4 level,cell viability and colony formation ability were increased(P<0.05).Conclusion ABCA1 can promote the ferroptosis in HepG2/SR cells,and increase the sensitivity of HepG2/SR cells to Sorafenib,which is mediated by reducing cell viability,downregu-lating SLC7A11 and GPX4 protein levels,and upregulating Fe2+and ROS levels through degradation of SLC7A11关键词
肝细胞癌/三磷酸腺苷结合盒转运体A1/铁死亡/索拉非尼/耐药性/溶质载体家族7成员11Key words
hepatocellular carcinoma/ATP-binding cassette transporter A1(ABCA1)/ferroptosis/Sorafenib/resistance/solute carrier family 7 member 11(SLC7A11)分类
临床医学引用本文复制引用
江策,刘昳,赵亚磊,常香荣..ABCA1对肝癌细胞索拉非尼耐药的影响及其机制[J].山西医科大学学报,2025,56(4):347-355,9.基金项目
陕西省自然科学基础研究计划项目(2022JQ-833) （2022JQ-833）
