[1]熊 涛,许旋旋,刘荟敏,等.水苏碱调节FOXO3-FOXM1信号轴对急性髓系白血病细胞增殖、凋亡和放疗敏感性的实验研究[J].现代检验医学杂志,2025,40(06):28-32.[doi:10.3969/j.issn.1671-7414.2025.06.006]
　XIONG Tao,XU Xuanxuan,LIU Huimin,et al.Experimental Study on the Effect of Stachydrine on Proliferation, Apoptosis and Radiosensitivity of AML Cells by Regulating FOXO3-FOXM1 Signaling Axis[J].Journal of Modern Laboratory Medicine,2025,40(06):28-32.[doi:10.3969/j.issn.1671-7414.2025.06.006]
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水苏碱调节FOXO3-FOXM1信号轴对急性髓系白血病细胞增殖、凋亡和放疗敏感性的实验研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年06期
页码:
28-32
栏目:
论著
出版日期:
2025-11-15

文章信息/Info

Title:
Experimental Study on the Effect of Stachydrine on Proliferation, Apoptosis and Radiosensitivity of AML Cells by Regulating FOXO3-FOXM1 Signaling Axis
文章编号:
1671-7414（2025）06-028-05
作者:
熊 涛1，许旋旋1，刘荟敏1，张江召1，王远丽1，张 敏2
1.荆州市中心医院血液内科，湖北荆州 434000;2.湖北中医药高等专科学校医疗系，湖北荆州 434000
Author(s):
XIONG Tao1，XU Xuanxuan1，LIU Huimin1，ZHANG Jiangzhao1，WANG Yuanli1，ZHANG Min2
1.Department of Pediatric Hematology, Jingzhou Central Hospital, Hubei Jingzhou 434000, China;2.Medical Department of Hubei University of Traditional Chinese Medicine, Hubei Jingzhou 434000, China
关键词:
水苏碱; 急性髓系白血病; 叉头框蛋白O3-叉头框蛋白M1信号轴; 增殖; 凋亡; 放疗敏感性
分类号:
R557；R446.113
DOI:
10.3969/j.issn.1671-7414.2025.06.006
文献标志码:
A
摘要:
目的探究水苏碱（STA）调节转录因子叉头框蛋白O3（FOXO3）-叉头框蛋白M1（FOXM1）信号轴对急性髓系白血病（AML）细胞增殖、凋亡和放疗敏感性的实验研究。方法?用浓度为50~1600μmol/L的STA处理人AML细胞（HL-60），用CCK-8法检测HL-60细胞活性，筛选最佳药物浓度；将HL-60细胞分为对照组（Control组）、水苏碱低、中、高浓度组（STA-L组，STA-M组，STA-H组）、水苏碱+慢病毒转染对照组（STA-H+LV-NC组）、水苏碱高浓度+FOXO3过表达慢病毒组（STA-H+LV-FOXO3组）。5-乙炔基脱氧尿苷（Edu）检测HL-60细胞增殖；流式细胞仪（FCM）检测细胞凋亡；细胞克隆实验检测细胞放疗敏感性；免疫印迹（Westernblot）检测细胞核增殖抗原标记物（Ki67）、细胞周期蛋白D1（CyclinD1）、半胱氨酸蛋白酶-3（Caspase-3）、B细胞淋巴瘤-2相关X蛋白（Bax），FOXO3和FOXM1蛋白表达。结果选择STA浓度为100，200和400μmol/L用于后续实验。与Control组比较，STA-L，STA-M，STA-H组Ki67，CyclinD1，Edu阳性率、FOXO3，FOXM1表达水平依次降低（tSTA-L=2.169～5.879，tSTA-M=3.089～11.284，tSTA-H=4.572～11.502），Caspase-3，Bax表达水平、细胞凋亡率依次升高（tSTA-L=9.171，10.082，20.144；tSTA-M=5.435，7.530，7.450；tSTA-H=4.138，4.159，5.956），差异具有统计学意义（均P<0.05）；与STA-H+LV-NC组相比，STA-H+LV-FOXO3组Edu阳性率、Ki67，CyclinD1，FOXO3，FOXM1表达水平显著升高（t=10.055～16.267），Bax，Caspase-3表达水平、细胞凋亡率显著降低（t=5.736，5.433，8.939），差异具有统计学意义（均P<0.05）。放疗组、STA+放疗组HL-60细胞克隆形成率随着放疗剂量的增加而降低，差异具有统计学意义（F=78.630，137.843，均P<0.05），且STA+放疗组HL-60细胞克隆形成率比放疗组同剂量低（t=1.480～11.301，均P<0.05）。结论水苏碱通过抑制FOXO3-FOXM1信号轴抑制AML细胞增殖、诱导凋亡、增强放疗敏感性。
Abstract:
Objective The effects of stachydrine (STA) on the proliferation, apoptosis and radiosensitivity of acute myeloid leukemia (AML) cells by regulating the transcription factor forkhead box protein O3 (FOXO3)-forkhead box protein M1 (FOXM1) signaling axis. Methods Human AML cells (HL-60) were treated with STA at a concentration of 50～1 600 μmol/L, and the activity of HL-60 cells was detected using the cell counting kit-8 (CCK-8) method to screen for the optimal drug concentration; HL-60 cells were separated into Control group, low, medium, and high concentration STA groups (STA-L group, STA-M group, STA-H group), STA+lentivirus transfection control group (STA-H+LV-NC group), and high-concentration STA+FOXO3 overexpression lentiviral group (STA-H+LV-FOXO3 group). 5-ethyny1-2’-deoxyuridine (Edu) was applied to detect HL-60 cell proliferation; flow cytometry(FCM) was applied to detect cell apoptosis; cell cloning experiments were applied to detect the radiotherapy sensitivity of cells; Western blot was applied to detect the expression of cell proliferation antigen markers (Ki67), Cyclin D1, Caspase-3, B-cell lymphoma2 assaciated X protein (Bax), FOXO3, and FOXM1 proteins. Results STA concentrations of 100, 200 and 400 μmol/L were selected for subsequent experiments. Compared with the control group, the positive rate of Ki67, Cyclin D1,Edu, FOXO3 and FOXM1 expression levels in the STA-L, STA-M, and STA-H groups decreased sequentially(tSTA-L=2.169～5.879, tSTA-M=3.089～11.284, tSTA-H=4.572～11.502), Caspase-3 and Bax expression levels, the apoptosis rate, increased sequentially (tSTA-L=9.171, 10.082, 20.144; tSTA-M=5.435, 7.530, 7.450; tSTA-H=4.138, 4.159, 5.956) and the differences were statistically significant (all P<0.05), respectively. Compared with the STA-H+LV-NC group, the positive rate of Edu and the expression levels of Ki67,Cyclin D1, FOXO3 and FOXM1 were obviously increased in the STA-H+LV-FOXO3 group(t=10.055～16.267), Caspase-3 and Bax expression levels, the apoptosis rate were obviously reduced (t=5.736, 5.433, 8.933), and the differences were statistically significant (all P<0.05), respectively. The colony formation rate of HL-60 cells in the radiotherapy group and STA+radiotherapy group decreased with the increase of radiotherapy dose, and the differences were statistically significant(F=78.630, 137.843, all P<0.05), and the colony formation rate of HL-60 cells in the STA+radiotherapy group was lower than that in the radiotherapy group at the same dose (t=1.480～11.301, all P<0.05). Conclusion Stachydrine inhibits AML cell proliferation, induces apoptosis, and enhances radiotherapy sensitivity by inhibiting the FOXO3-FOXM1 signaling axis.

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备注/Memo

备注/Memo:
作者简介：熊涛（1979-），男，硕士研究生，副主任医师，研究方向：血液系统恶性肿瘤性疾病及血液病危重症，E-mail：xiongtaojz@sina.com。
更新日期/Last Update: 2025-11-15