Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells
Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells
复制标题
白藜芦醇下调的磷酸化肝激酶B1参与急性髓系白血病干细胞的衰老
DOI：
10.1007/s11596-015-1457-7
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发表时间：
2015-08-01
影响因子：
--
通讯作者：
Liu, Ling-bo
中科院分区：
文献类型：
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作者：
Peng, Dan-yue;Song, Hui;Liu, Ling-bo
衰老是癌症发展的重要障碍。参与衰老反应可能是治疗急性髓性白血病（AML）的有效途径。本研究旨在探讨白藜芦醇下调磷酸化肝激酶B1 （pLKB1）对急性髓性白血病（AML）干细胞衰老的影响。Western blotting检测白藜芦醇（40 μmol/L）处理和未处理CD34+CD38−KG1a细胞中pLKB1和pLKB1调控因子Sirtuin 1 （SIRT1）的蛋白表达。检测衰老相关因素，包括实时荧光定量PCR检测p21 mRNA，衰老相关β-半乳糖苷酶（SA-β-gal）染色检测细胞形态，MTT法检测细胞增殖，流式细胞术检测细胞周期。流式细胞术检测细胞凋亡。结果表明，pLKB1在CD34+CD38−KG1a细胞中高表达，白藜芦醇可通过激活SIRT1下调pLKB1，诱导CD34+CD38−KG1a细胞衰老和凋亡。由此可见，白藜芦醇下调pLKB1参与了AML干细胞的衰老。
Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34+CD38−KG1a cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34+CD38−KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34+CD38−KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.