基于网络药理学探究虾青素防治乳腺癌的分子机制  

The regulation mechanism of astaxanthin on breast cancer based on network pharmacology

作　　者：张楠[1] 曹晓东[1] 朱浩[1] 杨冬冬 赵晨宇 王学梅[1] 张子英[1] ZHANG Nan;CAO Xiaodong;ZHU Hao;YANG Dongdong;ZHAO Chenyu;WANG Xuemei;ZHANG Ziying(Key Laboratory of Molecular Pathology,Molecular Epidemiology Laboratory,Inner Mongolia Medical University,Huhhot 010110,China)

机构地区：[1]内蒙古医科大学分子病理实验室慢性病分子流行病实验室,呼和浩特010110

出　　处：《生物学杂志》2021年第4期23-28,共6页Journal of Biology

基　　金：国家自然科学基金项目(81960603);内蒙古自治区自然科学基金项目(2020MS08136,2020BS08015);内蒙古自治区高等学校科学研究项目(NJZZ18100);内蒙古医科大学科技百万工程项目(YKD2017KJBW007);内蒙古医科大学青年创新项目(YKD2018QNCX021)。

摘　　要：应用Pharm Mapper在线数据库预测虾青素(astaxanthin,ASX)的作用靶点,并应用OMIM、TTD等在线数据库获取乳腺癌的作用靶点;将ASX的靶点与乳腺癌的疾病靶点取交集得到ASX抑制乳腺癌的靶点,通过Cytoscape 3.7.1软件构建作用靶点的蛋白相互作用网络图筛选关键靶点;利用GO和KEGG数据库对所有作用靶点进行基因功能富集分析和通路富集分析,以确定其关键作用通路,探讨ASX抑制乳腺癌的作用机制。采用MTT法检测ASX对乳腺癌4T1细胞增殖的影响,通过Western Blot法对p-AKT和PI3K表达水平进行检测。结果显示ASX抑制乳腺癌靶点共21个,并筛选出ADIPOQ、BECNI和PGR 3个核心靶点,通过基因功能及通路富集分析结果发现,ASX抑制乳腺癌主要涉及癌症通路、免疫系统及细胞因子等多个生物过程。细胞增殖结果发现150和300μmol/L的ASX对乳腺癌4T1细胞生长有显著的抑制作用。Western Blot结果显示ASX可显著降低AKT的磷酸化及PI3K的表达水平。因此推断ASX可能通过PI3K/AKT信号通路来预防乳腺癌。In this study,the ingredient targets of astaxanthin were predicted by Pharm mapper databases,and the targets of breast cancer were obtained by OMIM-Online Mendelian Inheritance in Man(OMIM)and Therapeutic Target Database(TTD);the direct target was obtained through intersection of astaxanthin targets and breast cancer targets,and the software of Cytoscape 3.7.1 was used to construct the protein-protein interaction networks of key targets;enrichment of gene function and pathways of all potential targets was conducted by Gene Ontology(GO)database and Kyoto Encyclopedia of Genes and Genomes(KEGG)database to explore the mechanism of astaxanthin for the inhibition of breast cancer.MTT was used to detectcell proliferation.The expression of p-AKT and PI3K was tested by Western Blot.There were 21 targets of astaxanthin inhibiting breast cancer and three core targets(ADIPOQ,BECNI and PGR).These targets were participated in critical pathway such as cancer pathway,immune system and cytokines to inhibit breast cancer.ASX of 150 and 300μmol/L significantly inhibited the growth of breast cancer 4T1 cells.ASX could significantly reduce the phosphorylation of AKT and the expression level of PI3K.Therefore,it was induced that astaxanthin could prevente breast cancer through the PI3K/AKT signaling pathway.

关 键 词：虾青素 乳腺癌 抑制 网络药理学 分子机制 

分 类 号：R285.5[医药卫生—中药学]