应用分子对接技术预测氟伐他汀对胰腺癌细胞作用的关键靶点  

Prediction of key targets of fluvastatin on pancreatic cancer cells by molecular docking

作　　者：朱秀贤[1] 杨舜娟[1] 林菁红[1] 甘惠贞[1] Zhu Xiuxian;Yang Shunjuan;Lin Jinghong;Gan Huizhen(Department of Pharmacy,The 910th Hospital of PLA,Quanzhou 362000,China)

机构地区：[1]中国人民解放军联勤保障部队第910医院药剂科,福建泉州362000

出　　处：《实用药物与临床》2022年第12期1057-1063,共7页Practical Pharmacy and Clinical Remedies

摘　　要：目的应用生物信息学综合考察氟伐他汀对胰腺癌MiaPaCa-2和PANC-1细胞基因表达谱的影响,并采用分子对接预测关键蛋白靶点。方法从基因芯片公共数据库中下载氟伐他汀处理胰腺癌MiaPaCa-2和PANC-1细胞的基因表达谱芯片数据,以P<0.05和|logFC|>1为标准,筛选差异表达基因互作关系。采用VennDiagram R包取交集,得到共同差异表达基因;应用clusterProfiler R包,进行GO和KEGG通路富集分析;Cytoscape软件将差异表达基因互作关系可视化并找出潜在的关键基因,采用分子对接软件Autodock Tools-1.5.6将预测得到的关键蛋白靶点与氟伐他汀进行分子对接分析,进一步研究氟伐他汀与靶蛋白的相互作用。结果20μM氟伐他汀处理48 h后,胰腺癌细胞MiaPaCa-2和PANC-1共同差异表达基因共27个,主要涉及DNA复制、DNA错配修复与重组、染色体凝缩以及胞质分裂等作用。KEGG通路富集分析结果显示,共同差异表达基因主要与嘧啶代谢、p53信号通路和细胞周期等相关。分子对接结果显示,氟伐他汀与EXO1、MCM10、CDC45和KIF14这4个蛋白靶点之间具有较低的结合自由能,结合稳定。结论氟伐他汀能够影响胰腺癌细胞MiaPaCa-2和PANC-1细胞基因表达谱。EXO1、MCM10、CDC45和KIF14可能是氟伐他汀治疗胰腺癌潜在的作用靶点。Objective To investigate the effect of fluvastatin on gene expression profile of pancreatic cancer MiaPaCa-2 and PANC-1 cells by bioinformatics,and to predict key protein targets by molecular docking.Methods The mRNA gene expression profile data of human pancreatic cancer cells MiaPaCa-2 and PANC-1 treated with fluvastatin was downloaded from Gene Expression Omnibus(GEO)public database,and the differentially expressed genes(DEGs)were screened based on|logFC|>1 and P<0.05.Differentially co-expressed genes were obtained by VennDiagram R package;GO and KEGG pathways were enriched and analyzed by clusterProfiler R package.Cytoscape was used to visualize the PPI network and predict hub genes.The hub genes were then docked with fluvastatin by AutodockTools-1.5.6 molecular docking software and the energy was calculated to evaluate the interaction between fluvastatin and target proteins.Results After exposure to 20μM fluvastatin for 48 hours,27 common DEGs of MiaPaCa-2 and PANC-1 cells were identified,mainly involving DNA replication,DNA mismatch repair and recombination,chromosome condensation and cytoplasmic division.The GO and KEGG analysis indicated that these common genes were associated with pyrimidine metabolism,p53 signaling pathway and cell cycle.The results of molecular docking showed that fluvastatin had low binding free energy and stable binding to EXO1,MCM10,CDC45 and KIF14.Conclusion Fluvastatin can affect the gene expression profile of pancreatic cancer cells MiaPaCa-2 and PANC-1.EXO1,MCM10,CDC45 and KIF14 may be potential targets of fluvastatin in the treatment of pancreatic cancer.

关 键 词：氟伐他汀 胰腺癌 分子对接 基因表达 生物信息学 

分 类 号：R96[医药卫生—药理学]