双氢青蒿素与三氧化二砷对急性髓系白血病细胞凋亡的影响
[Effect of Dihydroartemisinin and Arsenic Trioxide on Apoptosis of Acute Myeloid Leukemia Cells].
作者信息
Sun Wei-Dong, Wang Xin, Wang Ying, Tong Xiang-Min
机构信息
Department of Hematology, Shaoxing Central Hospital, Shaoxing 321030, Zhejiang Province, China; Key Laboratory of Molecular Diagnosis and Individualization of Cancer, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
Key Laboratory of Molecular Diagnosis and Individualization of Cancer, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Oct;30(5):1337-1342. doi: 10.19746/j.cnki.issn.1009-2137.2022.05.006.
OBJECTIVE
To investigate the effect of dihydroartemisinin (DHA) combined with arsenic trioxide (ATO) on the viability and apoptosis of acute myeloid leukemia (AML) FLT3-ITD mutant cell line MOLM13 and its mechanism.
METHODS
MOLM13 cells were treated with DHA or ATO alone or in combination. The viability of MOLM13 cells was detected by CCK-8 assay, cell proliferation was observed by colony formation assay, cell apoptosis and reactive oxygen species (ROS) level were measured by flow cytometry, and the expression levels of proteins related to apoptosis were detected by Western blot.
RESULTS
Compared with the control group, treatment with DHA and ATO alone or in combination could inhibit cell proliferation, activate ROS formation, and finally induce cell apoptosis. DHA in combination with ATO produced a synergistic effect. Western blot analysis showed that DHA combined with ATO could significantly upregulate the level of c-PARP and activate apoptosis via inhibition of Mcl-1 and FLT3-ITD.
CONCLUSION
DHA combined with ATO induces the apoptosis of FLT3-ITD AML cell line MOLM13 by inhibiting Mcl-1 pathway and activating FLT3-ITD protein degradation.
目的
探讨双氢青蒿素（DHA）联合三氧化二砷（ATO）对急性髓系白血病（AML）FLT3-ITD突变细胞系MOLM13活力及凋亡的影响及其机制。
方法
用DHA或ATO单独或联合处理MOLM13细胞。采用CCK-8法检测MOLM13细胞活力，通过集落形成试验观察细胞增殖，用流式细胞术检测细胞凋亡及活性氧（ROS）水平，并用蛋白质印迹法检测凋亡相关蛋白的表达水平。
结果
与对照组相比，单独或联合使用DHA和ATO处理均可抑制细胞增殖，激活ROS生成，并最终诱导细胞凋亡。DHA与ATO联合产生协同效应。蛋白质印迹分析表明，DHA联合ATO可显著上调c-PARP水平，并通过抑制Mcl-1和FLT3-ITD激活凋亡。
结论
DHA联合ATO通过抑制Mcl-1通路并激活FLT3-ITD蛋白降解诱导FLT3-ITD AML细胞系MOLM13凋亡。
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