人参皂苷 Rg1 通过激活沉默调节蛋白 1（SIRT1）/结节性硬化复合物 2（TSC2）信号通路抑制来源于 KG1α 急性髓系白血病细胞的 CD34+CD38- 白血病干细胞的增殖并诱导其衰老标志物的表达。
Ginsenoside Rg1 Inhibits Cell Proliferation and Induces Markers of Cell Senescence in CD34+CD38- Leukemia Stem Cells Derived from KG1α Acute Myeloid Leukemia Cells by Activating the Sirtuin 1 (SIRT1)/Tuberous Sclerosis Complex 2 (TSC2) Signaling Pathway.
机构信息
Department of Radiology, The First Affiliated Hospital of Dali University, Dali, Yunnan, China (mainland).
Key Laboratory of Insect Biomedicine Research and Development in Yunnan Province, Dali University, Dali, Yunnan, China (mainland).
出版信息
Med Sci Monit. 2020 Feb 10;26:e918207. doi: 10.12659/MSM.918207.
BACKGROUND Clinical relapse in acute myeloid leukemia (AML) is associated with the reduced treatment response of leukemia stem cells (LSCs). This study aimed to investigate the effects of the ginseng derivative, ginsenoside Rg1 (Rg1), on CD34+CD38- LSCs derived from KG1a human acute myeloid leukemia cells. MATERIAL AND METHODS CD34+CD38- LSCs were isolated from KG1a human acute myeloid leukemia cells by cell sorting. CD34+CD38- KG1alpha LSCs were divided into the control group and the Rg1 group (treated with Rg1). The cell counting kit-8 (CCK-8) assay evaluated the proliferation of CD34+CD38- KG1alpha LSCs and flow cytometry studied the cell cycle. The mixed colony-forming unit (CFU-Mix) assay and staining for senescence-associated beta-galactosidase (SA-ß-Gal) evaluated cell senescence. Expression of sirtuin 1 (SIRT1) and tuberous sclerosis complex 2 (TSC2) were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS CD34+CD38- KG1alpha LSCs were isolated at 98.72%. Rg1 significantly reduced the proliferation of CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05). Cells in the G0/G1 phase were significantly increased, and cells in the G2/M and S phase were significantly reduced compared with the control group (p<0.05). Rg1 significantly increased SA-ß-Gal and reduced CFU-Mix formation compared with the control group (p<0.05), significantly down-regulated SIRT1 expression in CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05), and significantly reduced TSC2 expression in CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05). CONCLUSIONS Rg1 inhibited cell proliferation and induced cell senescence markers in CD34+CD38- KG1alpha LSCs by activating the SIRT1/TSC2 signaling pathway.
背景
急性髓系白血病（AML）的临床复发与白血病干细胞（LSCs）的治疗反应降低有关。本研究旨在探讨人参衍生物人参皂苷 Rg1（Rg1）对来源于 KG1a 人急性髓系白血病细胞的 CD34+CD38-LSCs 的影响。
材料与方法
通过细胞分选从 KG1a 人急性髓系白血病细胞中分离 CD34+CD38-LSCs。将 CD34+CD38-KG1alpha LSCs 分为对照组和 Rg1 组（用 Rg1 处理）。细胞计数试剂盒-8（CCK-8）检测 CD34+CD38-KG1alpha LSCs 的增殖，流式细胞术研究细胞周期。混合集落形成单位（CFU-Mix）检测和衰老相关β-半乳糖苷酶（SA-ß-Gal）染色评估细胞衰老。采用 Western blot 和实时定量聚合酶链反应（qRT-PCR）检测沉默信息调节因子 1（SIRT1）和结节性硬化复合物 2（TSC2）的表达。
结果
CD34+CD38-KG1alpha LSCs 的分离率为 98.72%。与对照组相比，Rg1 显著降低 CD34+CD38-KG1alpha LSCs 的增殖（p<0.05）。与对照组相比，G0/G1 期细胞明显增加，G2/M 和 S 期细胞明显减少（p<0.05）。与对照组相比，Rg1 显著增加 SA-ß-Gal 并减少 CFU-Mix 形成（p<0.05），显著下调 CD34+CD38-KG1alpha LSCs 中的 SIRT1 表达（p<0.05），并显著降低 CD34+CD38-KG1alpha LSCs 中的 TSC2 表达（p<0.05）。
结论
Rg1 通过激活 SIRT1/TSC2 信号通路抑制 CD34+CD38-KG1alpha LSCs 的细胞增殖并诱导细胞衰老标志物。
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