CAJ | 학술논문

目的探讨慢性粒细胞白血病(CML)细胞株K562中硫氧还蛋白还原酶(TrxR)的活力及其新型抑制剂乙烷硒啉(BBSKE)体外抗白血病作用.方法应用胰岛素还原法检测K562细胞株及健康人骨髓单个核细胞中TrxR的活力.运用CCK-8法测定BBSKE对K562细胞的增殖抑制率.应用激光共聚焦显微镜、琼脂糖凝胶电泳以及Annexin V-FITC/PI双标记流式细胞术观察BBSKE的抗白血病作用.结果 K562细胞中TrxR的活性明显高于健康人骨髓单个核细胞,10 μmol/L BBSKE与K562细胞作用24 h,激光共聚焦显微镜可见典型的细胞凋亡表现,琼脂糖凝胶电泳后可见典型的DNA"梯"条带出现,流式细胞术检测凋亡率为(10.28±2.74)%;10 μmol/LBBSKE对CML患者原代细胞有诱导凋亡的作用,凋亡率为(5.70±0.48)%.结论慢性粒细胞白血病细胞株K562中TrxR活力高于健康人骨髓单个核细胞,BBSKE有抑制TrxR活力、抑制K562细胞增殖和诱导凋亡的作用,是治疗CML潜在的有效药物.
목적 탐토만성립세포백혈병(CML)세포주K562중류양환단백환원매(TrxR)적활력급기신형억제제을완서람(BBSKE)체외항백혈병작용.방법 응용이도소환원법검측K562세포주급건강인골수단개핵세포중TrxR적활력.운용CCK-8법측정BBSKE대K562세포적증식억제솔.응용격광공취초현미경、경지당응효전영이급Annexin V-FITC/PI쌍표기류식세포술관찰BBSKE적항백혈병작용.결과 K562세포중TrxR적활성명현고우건강인골수단개핵세포,10 μmol/L BBSKE여K562세포작용24 h,격광공취초현미경가견전형적세포조망표현,경지당응효전영후가견전형적DNA"제"조대출현,류식세포술검측조망솔위(10.28±2.74)%;10 μmol/LBBSKE대CML환자원대세포유유도조망적작용,조망솔위(5.70±0.48)%.결론 만성립세포백혈병세포주K562중TrxR활력고우건강인골수단개핵세포,BBSKE유억제TrxR활력、억제K562세포증식화유도조망적작용,시치료CML잠재적유효약물.
Objective To explore the activity of thioredoxin reductase (TrxR) in chronic myeloid leukemia cell line K562 and the anti-leukemia effect of BBSKE (a novel inhibitor of TrxR) in vitro. Methods The activity of TrxR on K562 cell lineage and fresh bone marrow cell from healthy adult was analyzed by insulin reduction assay. The inhibition of proliferation was measured by CCK-8 assay. The anti-leukemia effect of BBSKE was detected by laser scanning confocal microscope,agarose gel electrophoresis and flow cytometry with Annexin V -FITC/PI staining. Results TrxR activity of K562 cell lineage was significantly higher than that of normal bone marrow mononuclear cells. The apoptosis of K562 cells could be induced at concentrations of 10 μmol/L BBSKE after treated for 24 hours. The typical DNA "ladder" bans were observed by agarose gel electrophoresis. The apoptotic rates of K562 cells were (10.28±2.74) %. Application of 10 μmol/L BBSKE for 48 hours could also induce apoptosis of fresh bone marrow cell from chronic myeloid leukemia patients, and the apoptotic rates were (5.70±0.48) %. Conclusion TrxR activity in chronic myeloid leukemia cells was significantly higher than that of normal cells. BBSKE inhibits the TrxR activity and the proliferation of K562 by inducing apoptosis.It might be a potential medication for chronic myeloid leukemia.