中国肿瘤生物治疗杂志2026，Vol.33Issue(3)：243-251,9.DOI:10.3872/j.issn.1007-385x.2026.03.003
ACTL6A通过调控GPX4介导的铁死亡促进弥漫大B细胞淋巴瘤细胞多柔比星耐药
Study on the role of ACTL6A in promoting doxorubicin resistance in diffuse large B cell lymphoma cells by regulating GPX4-mediated ferroptosis
摘要
Abstract
Objective:To investigate the mechanism by which actin-like protein 6A(ACTL6A)regulates ferroptosis and contributes to doxorubicin(DOX)resistance in diffuse large B cell lymphoma(DLBCL)cells.Methods:The parental DLBCL cell line SU-DHL-4 cells and its DOX-resistant variant SU-DHL-4/DOX cells were cultured.Changes in the expression of ACTL6A were detected by qPCR and WB assay.SU-DHL-4/DOX cells with ACTL6A knockdown were constructed by transfecting plasmids carrying a short hairpin RNA targeting ACTL6A(sh-ACTL6A)or its negative control(sh-NC).The expression levels of ACTL6A and ferroptosis-related proteins,including glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and acyl-CoA synthetase long-chain family member 4(ACSL4),were measured using qPCR and WB.Chromatin immunoprecipitation(ChIP)and dual-luciferase reporter assays were performed to verify the targeting and regulatory relationship between ACTL6A and GPX4.SU-DHL-4/DOX cells were divided into Control,sh-NC,sh-ACTL6A,sh-NC+oe-GPX4,and sh-ACTL6A+oe-GPX4 groups.Corresponding plasmids were transfected into the cells.CCK-8 assay was used to detect cell survival rates of each group under different concentrations of DOX treatment.FerroOrange,Liperfluo,and DCFH-DA probes were used to detect ferrous ion(Fe2+)levels,lipid peroxidation,and reactive oxygen species(ROS)in each group of cells,respectively.A colorimetric method was used to measure the contents of glutathione(GSH)and malondialdehyde(MDA)in each group of cells.Results:Both ACTL6A mRNA and protein were highly expressed in SU-DHL-4/DOX cells(both P<0.05),compared to SU-DHL-4 cells.ACTL6A and GPX4 have a targeting binding relationship.Knockdown of ACTL6A significantly decreased the mRNA and protein expression of ACTL6A and GPX4 in SU-DHL-4/DOX cells(both P<0.05),indicating that ACTL6A regulates GPX4 expression.Knockdown of ACTL6A significantly inhibited the survival of SU-DHL-4/DOX cells,increased intracellular Fe2+,lipid peroxides,ROS,and MDA levels,and inhibited GSH production(all P<0.05).However,overexpression of GPX4 in ACTL6A-knockdown cells upregulated the mRNA and protein expression levels of GPX4 in SU-DHL-4/DOX cells(both P<0.05),increased cell survival rate,inhibited the production of intracellular Fe2+,lipid peroxides,ROS,and MDA,and increased GSH production(all P<0.05).Conclusion:ACTL6A is highly expressed in DOX-resistant DLBCL cells.By regulating GPX4 expression,ACTL6A inhibits ferroptosis and promotes drug resistance in DLBCL cells.关键词
肌动蛋白样6A/弥漫大B细胞淋巴瘤/多柔比星/铁死亡/谷胱甘肽过氧化酶4Key words
actin-like protein 6A(ACTL6A)/diffuse large B cell lymphoma(DLBCL)/doxorubicin(DOX)/ferroptosis/glutathione peroxidase 4(GPX4)分类
医药卫生引用本文复制引用
王铃,任昳敏,胡彩华,缪宗..ACTL6A通过调控GPX4介导的铁死亡促进弥漫大B细胞淋巴瘤细胞多柔比星耐药[J].中国肿瘤生物治疗杂志,2026,33(3):243-251,9.基金项目
国家自然科学青年基金(82303915) （82303915）
中国青年创业就业基金 （）
南通大学临床医学专项科研基金(2023JY001) （2023JY001）
