基于瘀毒互结病机理论探讨隐丹参酮联用三氧化二砷治疗胃癌的作用机制  

The Mechanism of cryptotanshinonc combined with arsenic trioxide in the treatment of gastric cancer

作　　者：杜仲燕[1] 鲁军 赵正奇[1] 张光霁[1] Du Zhongyan

机构地区：[1]浙江中医药大学,310053

出　　处：《浙江临床医学》2021年第6期771-774,共4页Zhejiang Clinical Medical Journal

基　　金：国家自然科学基金重点资助项目(82030119);国家自然科学基金青年资助项目(82004353);浙江省自然科学基金资助项目(LQ20H290005);浙江省中医药科技计划(2019ZQ010);浙江省医药卫生项目(2019KY113);浙江中医药大学科研基金项目(2019ZG49)。

摘　　要：目的探讨隐丹参酮联用三氧化二砷治疗胃癌的潜在靶点和分子作用机制3方法通过DrugBank预测并筛选隐丹参酮和三氧化二砷的作用把点,通过GeneCards、DisGeNet和OM1M筛选胃癌托点,并利用Cytoscape软件构建隐丹参S同联用三氧化二神治疗胃癌的成分和作用把点网络,采用STRING数据库构建PPI网络,利用RclusterProfiler进行把点的GO和KEGG分析。结果筛选得到隐丹参酮和三氧化二砷的39个把点,预测涉及胃癌的靶点38个,主要与RELA、CCND1、MAPK1等靶点有关,其中37个把点有相互作用关系,以P<0.05进行筛选,得到GO分析62条,其功能涉及泛素蛋白连接酶结合、泛素样蛋白连接酶结合等过程。筛选得到139条信号通路,其中前20条KEGG通路为TNF信号通路、细胞凋亡等相关通路。结论隐丹参酮联用三氧化二砷治疗胃癌可能是通过靶向RelA并促其泛素化,进而抑制NF-κB活化,有可能成为精准治疗的新型药物。Objective To explore the potential targets and molecular mechanism of cryptotanshinone combined with arsenic trioxide in the treatment of gastric cancer.Methods We predict and screen the targets of cryptotanshinone and arsenic trioxide through DrugBank,screen gastric cancer targets through GeneCards,DisGeNet and OMIM,and use Cytoscape software to construct a network of components and targets of cryptotanshinone combined with arsenic trioxide in the.treatment of gastric cancer,and use STRING database to construct PPI Network,use Rcluster Profiler for GO and KEGG analysis of targets.Results 39 targets of cryptotanshinone and arsenic trioxide were screened,and 38 targets were predicted to be involved in gastric cancer,mainly related to targets such as RELA,CCND1,and MAPK1.Among them,37 targets have an interaction relationship.Screening was performed at P<0.05.62 GO analyses were obtained,whose functions involve processes such as ubiquitin protein ligase binding and ubiquitin-like protein ligase binding.139 signal pathways were screened,among which the first 20 KEGG pathways were TNF signal pathway,apoptosis and other related pathways.Conclusion Cryptotanshinone combined with arsenic trioxide in the treatment of gastric cancer may target RelA and promote its ubiquitination,thereby inhibiting NF-κB activation,and may become a new type of drug for precise treatment.

关 键 词：隐丹参酮 三氧化二砷 胃癌 网络药理 作用机制 

分 类 号：R73[医药卫生—肿瘤]