运用细胞代谢组学策略探究蒲公英提取物的抗肿瘤作用机制

Analysis of anti-tumor mechanism of extract from taraxacum monogon based on cell metabonomics strategy

目的:基于细胞代谢组学分析探究蒲公英提取物抗肿瘤作用的可能机制。方法:采用CCK-8实验检测不同质量浓度(0、5、10、25、50、100、200、400、800 mg/L)的蒲公英提取物处理细胞24 h对人非小细胞肺癌A549细胞活力的影响。以25 mg/L蒲公英提取物处理A549细胞(干预组),未处理的A549细胞为空白对照。24 h后,检测细胞活力,基于超高效液相色谱-质谱联用技术对2组细胞样品进行代谢组学分析。采用主成分分析及正交偏最小二乘判别分析法对数据进行模式识别,分析2组的代谢谱差异,进一步筛选差异代谢物,并分析代谢途径以探讨抗肿瘤机制。结果:蒲公英提取物可抑制A549细胞活力,其作用随剂量升高有增强的趋势(P<0.001)。与空白对照组比较,干预组细胞活力受抑(P<0.05)。2组细胞的代谢谱差异有统计学意义,共筛选并鉴定出136种差异代谢物,其中50种差异代谢物上调,86种下调,主要涉及嘌呤代谢、嘧啶代谢以及氨基糖和核苷酸糖代谢3个代谢通路。结论:蒲公英提取物可抑制A549细胞活力,其机制可能与影响多种能量及氨基酸代谢,从而扰乱A549细胞的生长和增殖等生命活动有关。

Aim:To investigate the possible anti-tumor mechanism of extract from taraxacum monogon(ETM)based on the analysis of metabolic profile.Methods:The cellular viability of the human lung carcinoma A549 cells treated with different concentrations(0,5,10,25,50,100,200,400,800 mg/L)of ETM for 24 hours was detected by CCK-8 assay.A549 cells were treated with 25 mg/L ETM(intervention group),and the untreated A549 cells were used as blank control.After 24 hours,UPLC-MS was used to identify the differential metabolites between the 2 groups.Principal component analysis and orthogonal to partial squares discriminant analysis were performed to identify differences in metabolic profiles between the 2 groups,the potential biomarkers were selected and the metabolic pathway was analyzed to explore the anti-tumor mechanism.Results:ETM could inhibit the viability of A549 cells in a dose-dependent way(P<0.001).Compared with the blank control group,the cellular viability in the intervention group was inhibited(P<0.05).The metabolic profiles of the 2 groups were significantly different,and 136 differential metabolites were screened and identified,out of which,50 metabolites were up-regulated and 86 were down-regulated,mainly involving 3 metabolic pathways(purine metabolism,pyridine metabolism,amino sugar metabolism and nucleotide sugar metabolism).Conclusion:ETM can inhibit the cellular viability of A549 cells,which may disrupt the growth and proliferation of A549 cells and other life activities by affecting various energy metabolism and amino acid metabolism.