Objective: To investigate the effect of tripipartite motif 59 (TRIM59) expression interference on the chemosensitivity of daunorubicin (DNR) in chronic myeloid leukemia (CML) K562 cells and the related molecular mechanism.
Methods: The expressions of TRIM59 mRNA in bone marrow tissues of patients with CML and K562 cells were detected by RT-qPCR. Liposome-based transfection technology was used to transfect TRIM59-specific siRNA (si-TRIM59) into K562 cells which then were treated with DNR. The proliferation and apoptosis of cells were detected by CCK-8 assay and flow cytometry, respectively, and the expressions of apoptosis-related protein and Wnt/β-catenin signaling pathway-related protein were detected by Western blot.
Results: Compared with the bone marrow tissue of CML patients at the time of initial treatment, the expression of TRIM59 mRNA in bone marrow tissue of CML patients at the time of chemotherapy resistance was significantly increased (P <0.05). Compared with control group, the cell proliferation inhibition rate and apoptosis rate in si-TRIM59 group and DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased (P <0.05), while the expressions of Bcl-2, Wnt3α, GSK-3β protein and the ratio of p-β-catenin/β-catenin were significantly decreased (P <0.05). Compared with si-TRIM59 group and DNR group, the proliferation inhibition rate and apoptosis rate of si-TRIM59+DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased, while the expression of Bcl-2, Wnt3α, GSK-3β protein and the ratio of p-β-catenin/β-catenin were significantly decreased (P <0.05).
Conclusion: TRIM59 expression interference may enhance the chemosensitivity of K562 cells to DNR, and its mechanism may be related to the regulation of Wnt/β-catenin signaling pathway.
题目: 干扰TRIM59表达对慢性粒细胞白血病K562细胞柔红霉素化疗敏感性的影响及作用机制研究.
目的: 探讨干扰三元基序59（TRIM59）表达对慢性粒细胞白血病K562细胞柔红霉素（DNR）化疗敏感性的影响及相关分子机制。.
方法: 采用RT-qPCR法检测慢性粒细胞白血病患者骨髓组织和K562细胞中TRIM59 mRNA表达水平。用脂质体转染法将TRIM59特异性小干扰RNA（si-TRIM59）转染至K562细胞，并用DNR处理细胞。CCK-8法检测细胞增殖，流式细胞术检测细胞凋亡，Western blot法检测凋亡相关蛋白和Wnt/β-catenin信号通路相关蛋白表达。.
结果: 与初治时骨髓组织相比，化疗耐药时患者骨髓组织中TRIM59 mRNA表达水平升高（P <0.05）。与对照组比较，si-TRIM59组和DNR组细胞增殖抑制率、细胞凋亡率均显著升高（P <0.05）；细胞中Bax、Caspase3、Cleaved-Caspase3蛋白表达量均显著升高，而Bcl-2、Wnt3α、GSK-3β蛋白表达量、p-β-catenin/β-catenin比值均显著降低（P <0.05）。与si-TRIM59组和DNR组比较，si-TRIM59+DNR组细胞增殖抑制率、细胞凋亡率均显著升高（P <0.05）；细胞中Bax、Caspase3、Cleaved-Caspase3蛋白表达量均显著升高，而Bcl-2、Wnt3α、GSK-3β蛋白表达 量、p-β-catenin/β-catenin比值均显著降低（P <0.05）。.
结论: 干扰TRIM59表达可增强K562细胞对DNR的化疗敏 感性，其作用机制可能与调控Wnt/β-catenin信号通路相关。.
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