木犀草素抑制结直肠癌SW620细胞生长的蛋白质组学机制研究  

Investigation of Proteomic Mechanisms of Luteolin′s Inhibition on Growth of Colorectal Cancer SW620 Cells

作　　者：赵佳威 孟波 陆澳 韩梓星 叶子弘 赵洋 ZHAO Jia-Wei;MENG Bo;LU Ao;HAN Zi-Xing;YE Zi-Hong;ZHAO Yang(Zhejiang Provincial Key Laboratory of Biometrology and Inspection&Quarantine,College of Life Sciences,China Jiliang University,Hangzhou 310018,China;Technology Innovation Center of Mass Spectrometry for State Market Regulation,Center for Advanced Measurement Science,National Institute of Metrology,Beijing 100029,China)

机构地区：[1]中国计量大学生命科学学院,浙江省生物计量及检验检疫技术重点实验室,杭州310018 [2]中国计量科学研究院前沿计量科学中心,国家市场监管技术创新中心(质谱),北京100029

出　　处：《分析化学》2025年第2期258-268,共11页Chinese Journal of Analytical Chemistry

基　　金：科技基础资源调查专项项目(No.2022FY101202);国家重点研发计划项目(No.2022YFF0608400)资助。

摘　　要：随着结直肠癌发病率的持续攀升,患者群体呈年轻化趋势。现有治疗方案虽然能延长生存期,却不可避免地带来严重的副作用,因此,开发新型治疗策略势在必行。木犀草素(Luteolin,LUT)作为天然草药活性成分,其广谱抗肿瘤效应在多种癌症研究中得到了证实,然而其对结直肠癌的作用机制尚未明确。本研究从蛋白质组-糖蛋白质组协同调控角度揭示了LUT对结直肠癌SW620细胞的分子作用机制。采用蛋白质组学分析鉴定出472个差异表达的蛋白质。功能富集分析显示,下调蛋白质主要参与氧化应激反应、mRNA处理、RNA剪接以及肌动蛋白纤维组织等关键生物过程,并涉及氧化磷酸化和过氧化物酶体通路;而上调蛋白质则主要参与DNA复制、蛋白质折叠及rRNA代谢等过程,与DNA复制和内质网中蛋白质加工通路密切相关。在糖蛋白质组学层面,本研究发现了231条差异表达的完整N-糖肽。对应糖蛋白的功能富集分析表明,LUT可能通过调节核组织、核膜组织和Fc受体介导的刺激信号通路等生物过程,以及内质网蛋白质加工和N-糖基化生物合成通路发挥生物学效应。关键互作网络分析鉴定出5个核心靶蛋白,分别为RPS15A、WDR43、FBL、UTP18和UTP11,这些蛋白缺失已被证实可抑制多种肿瘤细胞增殖和迁移。值得注意的是,溶酶体相关膜蛋白LAMP1和LAMP2的糖基化修饰改变提示LUT可能通过调控细胞器动态影响肿瘤转移潜能。本研究结果揭示了LUT可通过特异性调控蛋白表达网络与糖基化修饰模式双重机制抑制结肠癌细胞恶性表型,为基于天然产物的结直肠癌精准治疗提供了新型分子靶标和理论依据。With the continuous rise in the incidence of colorectal cancer and the trend towards younger patient population,the existing treatment options,while able to prolong survival,are difficult to avoid significant side effects.It is imperative to develop new treatment strategies.Luteolin(LUT),as a natural herbal active ingredient,has been proved to have broad-spectrum anti-tumor effects in studies of multiple cancer types.However,the mechanism of LUT action in colorectal cancer has not been systematically elucidated.In this study,for the first time,the molecular mechanism of LUT on colorectal cancer SW620 cells from the perspective of proteomicsglycoproteomics co-regulation was revealed.Proteomic analysis identified 472 differentially expressed proteins.Functional enrichment analysis showed that down-regulated proteins were mainly involved in oxidative stress response,mRNA processing,RNA splicing,and actin filament organization among key biological processes,involving oxidative phosphorylation and peroxisome pathways.Up-regulated proteins were mainly involved in DNA replication,protein folding,and rRNA metabolism,closely related to DNA replication and protein processing pathways in the endoplasmic reticulum.At the level of glycoproteomics,231 differentially expressed intact N-glycopeptides were identified.Functional enrichment analysis of corresponding glycoproteins indicateed that LUT might exert biological effects by regulating biological processes such as nuclear organization,nuclear membrane organization,and Fc receptor-mediated signaling pathways,as well as endoplasmic reticulum protein processing and N-glycan biosynthesis pathways.Analysis of key interaction networks revealed 5 core target proteins namely RPS15A,WDR43,FBL,UTP18,and UTP11.The loss of these proteins had been confirmed to inhibit the proliferation and migration of various tumor cells.Notably,altered glycosylation modifications of the lysosome-associated membrane proteins LAMP1 and LAMP2 suggested that LUT might affect tumor metastatic potential by

关 键 词：结直肠癌 木犀草素 蛋白质组学 糖蛋白质组学 

分 类 号：R735.34[医药卫生—肿瘤]