首页|基于LC-MS技术探讨仙鹤草干预非小细胞肺癌A549细胞的代谢组学研究

基于LC-MS技术探讨仙鹤草干预非小细胞肺癌A549细胞的代谢组学研究

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本研究应用体外细胞实验分析仙鹤草(Agrimonia pilosa,AP)干预A549细胞后,A549细胞的细胞活力、细胞凋亡、细胞周期的变化,探讨仙鹤草在体外的抗肿瘤活性,同时利用液相色谱-质谱(liquid chromatography-mass spectrometry,LC-MS)联用的代谢组学技术分析细胞内代谢物的变化及代谢通路,为研究仙鹤草治疗非小细胞肺癌A549细胞的作用机制提供理论基础和实验依据.实验结果显示随着仙鹤草药物浓度的增加,A549细胞的细胞核发生皱缩,出现明显的凋亡现象;细胞的存活率降低,在低、高剂量条件下抑制率分别达到21.5%、91.74%;乳酸脱氢酶(lactate dehydrogenase,LDH)含量上升(P<0.05).代谢组学结果显示两组间代谢差异明显,推测出LysoPC(24∶0/0∶0)、LysoPC(17∶0/0∶0)和PC(O-40∶5)等33个差异代谢物;通路富集发现,中药仙鹤草主要通过调节A549细胞的甘油磷脂代谢、嘌呤代谢等发挥抗肿瘤作用,其中对甘油磷脂代谢通路的影响最为显著.结合药效结果提示,仙鹤草有可能通过调节A549细胞内LysoPC(24∶0/0∶0)、LysoPC(17∶0/0∶0)和PC(O-40∶5)代谢物,诱导细胞凋亡和抑制A549细胞的生长.
Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells
The objective of this study was to analyze the effects on cell viability,apoptosis,and cell cycle of non-small cell lung cancer(NSCLC)A549 cells after intervention with Agrimonia pilosa(AP)and investigate Agrimonia pilosa anti-tumor activity in vitro.Meanwhile,liquid chromatography mass spectrometry(LC-MS)metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways.The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells.The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration.The survival rate of the cells decreased,and the inhibition rate reached 21.5%and 91.74%under the low and high dose conditions,respectively.Lactate dehydrogenase(LDH)content increased(P<0.05).Metabolomics results showed significant differences in metabolism between groups,thirty-three distinct metabolites including LysoPC(24∶0/0∶0),LysoPC(17∶0/0∶0)and PC(O-40∶5)were deduced.The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells,in which the effect on glycero-phosphate metabolism pathway was most significant.The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24∶0/0∶0),LysoPC(17∶0/0∶0)and PC(O-40∶5)metabolites in A549 cells.

AgrimoniapilosametabolomicsA549 cellapoptosiscell cycle

同泽华、郭文军、邹瀚锐、徐丽伟、徐雅娟、王卫芳

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长春中医药大学,吉林长春 130117

长春中医药大学附属医院,吉林长春 130021

吉林省中医药科学院,吉林长春 130012

仙鹤草 代谢组学 A549细胞 细胞凋亡 细胞周期

吉林省科技发展计划吉林省自然科学基金国家级大学生创新创业训练计划国家级大学生创新创业训练计划吉林省中医药局科研项目

YDZJ202201ZYTS1812022101990262022101990272020053

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(3)
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