中南医学科学杂志2025，Vol.53Issue(2)：211-216,6.DOI:10.15972/j.cnki.43-1509/r.2025.02.005
SFXN2介导的线粒体自噬参与弥漫性大B细胞淋巴瘤的利妥昔单抗耐药机制研究
Study on the role of SFXN2-mediated mitophagy in the mechanism of rituximab resistance in diffuse large B-cell lymphoma
摘要
Abstract
Aim To explore the mechanism of rituximab resistance in diffuse large B-cell lymphoma(DLBCL)through mi-tochondrial autophagy mediated by sideroflexin 2(SFXN2).Methods The DLBCL cell lines(OCI-LY1 and RL)and rituximab resistant cell lines(RL-4RH)were divided into Vector/OCI-LY1 group,SFXN2/OCI-LY1 group,short hairpin SFXN2(shSFXN2)/RL group and its negative control(shNC)/RL group,shNC/RL-4RH group,shSFXN2/RL-4RH group,mitochondrial autophagy in-hibitor Chloroquine(CQ)/RL-4RH group,and CQ+shSFXN2/RL-4RH group in this study.The expression level of SFXN2 protein in each group was compared.CCK-8 and FACS were used to analyze cell viability and apoptosis in each group.Autophagy flux of RL-4RH cells after knocking down SFXN2 was observed under laser confocal microscopy.The nude mice were divided into RL group(inoculated with RL tumor cells),RL-4RH group(inoculated with RL-4RH tumor cells),and RL-4RH+shSFXN2 group(inoculated with shSFXN2 transfected RL-4RH tumor cells).After intervention with rituximab,the expression of Ki67 and SFXN2 in tumor tis-sues of each group was analyzed by immunohistochemical staining.Results Compared with the shNC/RL group,the shSFXN2/RL group showed a decrease in SFXN2 protein expression level and cell viability(P＜0.05),but an increase in cell apoptosis rate(P＜0.05).Compared with the Vector/OCI-LY1 group,the SFXN2 protein expression level and cell viability were increased in the SFXN2/OCI-LY1 group(P＜0.05).Compared with the shNC/RL-4RH group,the shSFXN2/RL-4RH group showed a decrease in autophagosomes(P＜0.05),but an increase in the number of autophagic vacuoles and autolysosomes(P＜0.05).Compared with the shSFXN2/RL-4RH group,the CQ+shSFXN2/RL-4RH group showed an increase in autophagosomes(P＜0.05)but a decrease in the number of autolysosomes(P＜0.05).Compared with the RL group,the RL-4RH group showed an increase in tumor volume in tumor bearing mice(P＜0.05),and upregulation of SFXN2 and Ki67 expression in tumor tissue(P＜0.05);Knockdown of SFXN2 reversed the rituximab resistance effect in RL-4RH tumor bearing mice(P＜0.05).Conclusion Knockdown of SFXN2 may reverse ritux-imab resistance by inducing excessive activation of mitochondrial autophagy.关键词
铁氧蛋白2/线粒体/自噬/弥漫性大B细胞淋巴瘤/利妥昔单抗/耐药Key words
sideroflexin 2/mitochondrial/autophagy/diffuse large B-cell lymphoma/rituximab/resistance分类
医药卫生引用本文复制引用
胡陶,杜春燕,李正斯..SFXN2介导的线粒体自噬参与弥漫性大B细胞淋巴瘤的利妥昔单抗耐药机制研究[J].中南医学科学杂志,2025,53(2):211-216,6.基金项目
四川省医学科研课题(s19068) （s19068）
绵阳市卫健委课题(201913) （201913）
