运用细胞代谢组学策略探究薯蓣皂苷元的抗肿瘤作用机制

目的:应用基于UPLC-MS/MS的细胞代谢组学研究策略,从肿瘤细胞整体层面探究薯蓣皂苷元的抗肿瘤作用机制。方法:采用噻唑蓝法考察薯蓣皂苷元对12种肿瘤细胞的抑制作用,获得相应的半抑制浓度(IC_(50)),检测分析薯蓣皂苷元干预48 h后细胞内的代谢物,采用化学计量学和多维数据统计方法比较干预后的细胞与空白组细胞代谢物的差异,并分析其代谢通路。结果:在薯蓣皂苷元的干预下,细胞内共有11种代谢物发生了显著变化,主要涉及丙氨酸、天冬氨酸和谷氨酸代谢,氨酰-tRNA的生物合成,谷氨酰胺和谷氨酸代谢,嘌呤代谢,精氨酸和脯氨酸代谢5条代谢通路;薯蓣皂苷元对于不同细胞系的抑制作用差异显著。结论:该研究丰富了薯蓣皂苷元的体外抗肿瘤谱,在体外细胞水平和代谢通路上提供了该药物抗肿瘤作用的可能机制,为薯蓣皂苷元的后续肿瘤药理学研究提供实验依据。

Analysis of Antitumor Mechanism of Diosgenin by Cell Metabonomics Strategy

Objective: To investigate the antitumor mechanism of diosgenin from the overall level of tumor cells by cell metabonomics strategy based on UPLC-MS/MS.Method: The anticancer effect of diosgenin on 12 kinds of human tumor cells was determined by methyl thiazol tetrazolium(MTT) assay and the corresponding half-inhibitory concentration(IC₅₀) was obtained.After treatment with or without diosgenin for 48 h,the cells were collected and analyzed by UPLC-MS/MS,followed by multivariate data analysis and pathway analysis.Result: Under the intervention of diosgenin,11 metabolites were identified as candidates for tumor cells.Pathway analysis revealed that the changes of metabolites mainly related to alanine,aspartate and glutamate metabolism,biosynthesis of aminoacyl-tRNA,glutamine and glutamate metabolism,purine metabolism,arginine and proline metabolism.Meanwhile,the inhibitory effect of diosgenin on 12 kinds of human tumor cells was significantly different.Conclusion: These findings enrich the antitumor spectrum of diosgenin and provide its potential antitumor mechanism from in vitro cell level and metabolic pathway.This study can provide experimental basis for further tumor pharmacology of diosgenin.