虎杖苷对骨髓增生异常综合征细胞株SKM-1细胞增殖的抑制作用及机制
Inhibitory effects and mechanism of Polydatin on proliferation of myelodysplastic syndrome derived cell line SKM-1 cells
凌志明 1王洪志 1杜宇 1许勇钢 1周庆兵2
作者信息
- 1. 中国中医科学院西苑医院血液病研究所,北京 100091
- 2. 中国中医科学院西苑医院老年医学研究所,北京 100091
- 折叠
摘要
目的:探讨虎杖苷对骨髓增生异常综合征(MDS)细胞株SKM-1细胞的增殖、细胞周期及凋亡的作用及可能的作用机制.方法:CCK-8法检测虎杖苷(0、25、50、100、200 µmol/L)对SKM-1细胞的抑制作用;碘化丙啶(PI)染色法检测虎杖苷(0、10、30 µmol/L)对SKM-1细胞周期的影响;流式细胞仪检测虎杖苷(0、10、30 μmol/L)对SKM-1细胞凋亡的作用;运用RNA-seq技术观察虎杖苷(0、30 µ mol/L)对SKM-1细胞全基因组范围内的基因表达作用,并对差异表达基因进行KEGG分析.结果:与空白组比较,不同浓度虎杖苷对SKM-1细胞具有显著的抑制作用(P＜0.05);10、30 μmol/L虎杖苷显著降低G0/G,期细胞比例,增加S期细胞比例(P＜0.05);30 μmol/L虎杖苷显著增加晚期与早期凋亡细胞的比例(P＜0.05);RNA-seq显示,与DMSO控制组比较,30 µmol/L虎杖苷能显著引起SKM-1细胞基因组的表达变化,共有174个差异表达基因(145高表达基因与29个低表达基因),KEGG分析显示,差异表达基因涉及细胞因子受体互动,趋化因子信号通路,PPAR-γ信号通路等.结论:虎杖苷能有效抑制SKM-1细胞的增殖并使细胞阻滞于S期,诱导细胞凋亡,其机制可能是通过调控相关基因的表达进而影响细胞因子受体互动、趋化因子信号通路、PPAR-γ信号通路等的功能而实现的.
Abstract
Objective:To investigate the effects of polydatin on proliferation,cell cycle and apoptosis of myelodysplastic syndrome(MDS)derived cell line SKM-1 cells,and explore its possible mechanism.Methods:CCK-8 assay was used to detect the inhibitory effect of polydatin(0,25,50,100,200 μmol/L)on SKM-1 cells.Propidium iodide(PI)staining was used to detect the effects of polydatin(0,10,30 μmol/L)on SKM-1 cell cycle.The effect of polydatin(0,10,30 μmol/L)on cell apoptosis of SKM-1 cells was detected by flow cytometry.RNA-seq technology was applied to observe the change of genome-wide gene expression in SKM-1 cells after treatment with polydatin at 0 and 30 μmol/L respectively,and the differentially expressed genes(DEGs)were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Results:Compared with those in the blank group,polydatin with different concentrations had significant inhibitory effect on SKM-1 cells(P＜0.05).The proportion of cells in G0/G,phase was decreased,and the proportion of cells in S phase was increased by polydatin at 10,30 µmol/L(P＜0.05).Polydatin at 30 μ.mol/L could increase the proportion of late and early apoptotic cells(P＜0.05).Compared with those in DMSO control group,RNA-seq showed that polydatin at 30 μmol/L could significantly change the gene expression in SKM-1 cells.We identified a total of 174 DEGs including 145 up-regulated and 29 down-regulated genes.KEGG database analysis showed that these DEGs were mainly involved in cytokine receptor interaction,chemokine signaling pathway,PPAR-γ signaling pathway and so on.Conclusion:Polydatin could effectively inhibit the proliferation of SKM-1 cells,arrest the cells in S phase,and induce cell apoptosis,which may be achieved by regulating the expression of related genes and affecting the functions of cytokine receptor interaction,chemokine signaling pathway and PPAR-γ signaling pathway.
关键词
骨髓增生异常综合征/虎杖苷/细胞周期/细胞凋亡/全基因组表达测序Key words
Myelodysplastic syndromes/Polydatin/Cell cycle/Cell apoptosis/Whole-genome expression sequencing引用本文复制引用
基金项目
北京市自然科学基金青年基金(7174344)
中国中医科学院优秀青年项目(ZZ13-YQ-010)
出版年
2024
国家科技期刊平台
NSTL
万方数据