医学分子生物学杂志2025，Vol.22Issue(4)：325-331,7.DOI:10.3870/j.issn.1672-8009.2025.04.004
MCL1调控GSK3β/Wnt/β-catenin信号轴促进急性T淋巴细胞白血病细胞对维奈克拉耐药的机制研究
MCL1 Promotes Drug Resistance of Acute T Lymphoblastic Leukemia Cells to Venetoclax by Regulating GSK3β/Wnt/β-Catenin Axis
摘要
Abstract
Objective To investigate the molecular mechanism by which myeloid cell leukemia factor 1(MCL1)promotes the resistance of acute T lymphoblastic leukemia(T-ALL)cells to venetoclax.Methods T-ALL parental cell line Jurkat and T-ALL venetoclax-resistant cell line Jur-kat/VEN were cultured,and small interfering RNA targeting MCL1(si-MCL1)and negative con-trol(si-NC)were transfected into Jurkat/VEN cells.RT-qPCR and Western blotting were used to detect the expression level of MCL1 in transfected cells to verify the transfection effect.The expres-sion levels of GSK3β,phosphorylated GSK3β(p-GSK3β),β-catenin,c-Myc,and cyclin D1 were detected by Western blotting.Jurkat/VEN cells were divided into 4 groups:control group,si-NC group,si-MCL1 group,si-MCL1+CHIR-99021 group.The CCK-8 method was used to detect the survival rate of Jurkat/VEN cells in each group under different concentrations(0,100,200,300,400,500 nmol/L)of venetoclax,the colony formation assay was used to detect the number of colonies formed in each group,and the flow cytometry was used to detect the apoptosis rate.Results Compared with those in the Jurkat cells,the protein expression level of MCL1 in the Jurkat/VEN cells was increased(P＜0.05),the expression level of GSK3 β was decreased(P＜0.05),and the expression levels of p-GSK3β,β-catenin,c-Myc and Cyclin D1 were increased(P＜0.05).Compared with those in the control group and si-NC group,the mRNA and protein expression levels of MCL1 were decreased in the si-MCL1 group(P＜0.05),the expression level of GSK3β was increased(P＜0.05),and the expression levels of p-GSK3β,β-catenin,c-Myc and Cyclin D1 proteins were decreased(P＜0.05).Compared with those in the control group and si-NC group,the survival rate after venetoclax treatment and the value of IC50 were decreased in the si-MCL1 group(P＜0.05),the number of colonies was decreased(P＜0.05),and the apoptosis rate was increased(P＜0.05).Compared with those in the si-MCL1 group,the survival rate after venetoclax treatment and the value of IC50 were increased in the si-MCL1+CHIR-99021 group(P＜0.05),the number of colonies was increased(P＜0.05),and the apoptosis rate was decreased(P＜0.05).Conclusion Interference in MCL1 expression can reduce the drug resistance of Jurkat/VEN cells to venetoclax,which may be achieved by blocking the GSK-3β/Wnt/β-catenin signaling axis.关键词
急性T淋巴细胞白血病/髓样细胞白血病因子1/维奈克拉/耐药Key words
acute T lymphocytic leukemia/myeloid cell leukemia factor 1/venetoclax/drug resistance分类
医药卫生引用本文复制引用
马丽娜,郝建萍,张瑞,迪丽娜孜·阿不来提,赵芳,江明..MCL1调控GSK3β/Wnt/β-catenin信号轴促进急性T淋巴细胞白血病细胞对维奈克拉耐药的机制研究[J].医学分子生物学杂志,2025,22(4):325-331,7.基金项目
新疆维吾尔自治区自然科学基金(No.2022D01C754) This work was supported by a grant from the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C754) （No.2022D01C754）
