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基于细胞代谢组学技术探讨淫羊藿苷抑制人前列腺癌PC-3细胞增殖的机制

Mechanism of icariin inhibiting the proliferation of human prostate cancer PC-3 cells:An exploration based on cell metabolomics
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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。 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 analysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst database.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were identified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphatidylethanolamine,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 lysophosphatidylethanolamine,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.
作者 王涛 王伟 熊文俊 张子敬 王飞 彭耀辉 陈妍 曾海平 罗立杰 WANG Tao;WANG Wei;XIONG Wen-jun;ZHANG Zi-jing;WANG Fei;PENG Yao-hui;CHEN Yan;ZENG Hai-ping;LUO Li-jie(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510405,China;Guangdong Clinical Research Institute of Chinese Medicine,Guangzhou,Guangdong 510405,China;Changshan County Hospital of Chinese Medicine,Quzhou,Zhejiang 324200,China)
出处 《中华男科学杂志》 CAS CSCD 2024年第11期963-973,共11页 National Journal of Andrology
基金 国家自然科学基金青年项目(82205109) 广东省中医药局项目(20211199) 广州中医药大学第一附属医院中青年骨干培育项目(09005650055) 广州中医药大学第一附属医院国家中医药传承创新中心科研专项(2023QN11) 广州中医药大学第一附属医院配套科研经费(09005647001)。
关键词 淫羊藿苷 PC-3细胞 甘油磷脂代谢 氨基酸代谢 细胞代谢组学 icariin PC-3 cell glycerophospholipid metabolism amino acid metabolism cell metabolomics
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