基于网络药理学探讨苦参对人结肠癌细胞增殖及p53蛋白表达的影响机制  

Effects of Kushen(Sophora flavescens)on proliferation and p53 protein expression of human colon cancer based on network pharmacology

作　　者：张天泽 宋娟 尹传华 杜楠 刘春杰 王利宁 李克明[5] 张贺 ZHANG Tianze;SONG Juan;YIN Chuanhua;DU Nan;LIU Chunjie;WANG Lining;LI Keming;ZHANG He(School of Traditional Chinese Medicine,Beijing University of Traditional Chinese Medicine,Beijing 100029,China;不详)

机构地区：[1]北京中医药大学中医学院,北京100029 [2]滕州市中医医院肛肠科 [3]沂南县人民医院普外科 [4]乳山市人民医院肿瘤科 [5]山东省中医药研究院药理研究所 [6]山东中医药大学附属医院药学部

出　　处：《山东医药》2022年第28期38-42,共5页Shandong Medical Journal

基　　金：青岛大学医疗集团科研专项(YLJT20212020);山东省医学会临床科研专项(YXH2019ZX018)。

摘　　要：目的观察苦参碱对于人结肠癌细胞株HT-29增殖及p53蛋白表达的影响,探讨中药苦参治疗结肠癌的作用机制。方法选取人结肠癌细胞株HT-29,用IL-6处理造模后加不同浓度苦参碱干预,并设置空白对照组,检测IL-6处理模型组及不同浓度苦参碱干预各组HT-29细胞活力及p53蛋白表达情况。通过网络检索TCMSP、OMIM和Disgenet三个数据库得到苦参主要活性成分及对应疾病的靶点,运用String数据库及Cytoscape软件将苦参对结肠癌的潜在靶点构建PPI,将药物疾病共同基因导入Metasacpe数据平台进行GO和KEGG富集分析。结果人结肠癌细胞株HT-29模型组细胞活力较空白组增强,p53蛋白表达水平下降;经苦参碱干预后各组细胞活力明显降低,p53蛋白表达水平增高。通过网络检索数据库共检索出苦参的45个有效成分和22个潜在作用靶点,检索出的治疗通路主要有VEGF信号通路、癌症通路、晚期糖基化产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路等。结论苦参能抑制结肠癌细胞增殖,并提高抗肿瘤基因p53蛋白的表达;其机制为苦参中抗癌活性成分通过多种信号通路作用于p53、IL-6、AKT1、PTGS2等靶点,从而对结肠癌起到干预作用。Objective To observe the effects of matrine on proliferation and p53 protein expression in human colon cancer cell line HT-29,and to explore the therapeutic mechanism of Chinese medicine matrine on colon cancer.Methods The human colon cancer cell line HT-29 was selected.After the cells were well cultured and grown,they were divided into the blank group(without any drugs),the model group[10 ng/mL of interleukin-6(IL-6)],the 4 ng/mL matrine combination group(10 ng/mL of IL-6 combined with 4 ng/mL matrine),and the 10 ng/mL matrine combination group(10 ng/mL of IL-6 combined with 10 ng/mL matrine),respectively.Cell viability and p53 protein expression in each group were detected after a period of intervention.The main active ingredients of matrine and corresponding disease targets were obtained by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Online Mendelian Inheritance in Man(OMIM)and DisGeNET databases.Protein-protein interaction(PPI)was constructed from the potential targets of matrine on colon cancer using string database and Cy to scape software,and the common genes of drug disease were imported into the metasacpe data platform for Gene Ontology(GO)and Kyoto Encyclopedia of genes and genes(KEGG)enrichment analysis.Results Compared with the blank group,the cell viability was enhanced,and the protein expression level of p53 decreased in the model group.After treatment with matrine,the cell viability of each group significantly decreased,and the protein expression level of p53 increased.A total of 45 active ingredients and 22 potential action targets of Kushen were retrieved through a web search database,and the retrieved therapeutic pathways mainly included vascular endothelial growth factors(VEGFs),cancer pathway,advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE)signaling pathway,and so on.Conclusion Kushen can inhibit the proliferation of colon cancer cells and improve the expression of p53 protein;its mechanism may be that

关 键 词：结肠肿瘤 苦参 细胞增殖 P53蛋白 网络药理学 

分 类 号：R735.3[医药卫生—肿瘤]