摘要
目的:基于细胞代谢组学技术研究淫羊藿苷抑制人前列腺癌PC-3细胞增殖的作用机制.方法:应用MTT法测定细胞增殖活性,与对照组和5-氟尿嘧啶组比较淫羊藿苷干预对PC-3细胞增殖的影响.采用Bligh-Dyer法提取干预后细胞内源性代谢物,运用超高压液相色谱串联四级杆飞行时间质谱技术分析代谢轮廓,结合主成分分析和正交偏最小二乘判别分析筛选差异代谢物并鉴定结构,基于MetaboAnalyst数据库富集代谢通路.结果:淫羊藿苷显著抑制人前列腺癌PC-3细胞增殖.本研究共筛选了 89个差异代谢物,主要为氨基酸、磷脂酰胆碱、磷脂酰乙醇胺、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺类成分.差异代谢物在淫羊藿苷干预后均有恢复至正常水平的趋势.淫羊藿苷显著下调PC-3细胞中磷脂酰胆碱、磷脂酰乙醇胺、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺等甘油磷脂类代谢物的代谢水平,显著上调色氨酸、亮氨酸、脯氨酸等氨基酸类代谢物的代谢水平.结论:淫羊藿苷抑制人前列腺癌PC-3细胞增殖可能与调节脂质代谢(甘油磷脂代谢)和氨基酸代谢密切相关.
Abstract
Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.
维普
万方数据