基于网络药理学探讨荔枝核“...同治”胃癌和肝癌的作用机制_尹硕鑫.pdf

论著生物信息技术基金项目:国家自然科学基金(81360531);广西自然科学基金(2020GXNSFAA238030);广西中医药大学研究生教育创新计划项目(YCSZ2022018)作者简介:尹硕鑫(1995 )，男，在读硕士研究生，研究方向:消化系统疾病的诊治。通信作者:陈远能(1964 )，男，博士，教授，研究方向:消化系统肿瘤的防治。基于网络药理学探讨荔枝核“异病同治”胃癌和肝癌的作用机制尹硕鑫1卢鑫1王舒萍1李安过1邱薛竹1李升驰1黄鸿翔1张涛2陈远能2(1 广西中医药大学研究生院，广西南宁市530000;2 广西中医药大学附属瑞康医院消化内科，广西南宁市530011)【摘要】目的基于网络药理学探索荔枝核“异病同治”胃癌和肝癌的作用机制。方法利用中药系统药理学数据库与分析平台搜索荔枝核的有效化学成分及其作用靶点，利用GeneCards 数据库、OMIM 数据库获得胃癌和肝癌相关靶点，将胃癌和肝癌相关靶点和荔枝核有效化学成分的作用靶点取交集后得到共同靶点。借助 STING 平台和 CytoScape 372 软件构建共同靶点的蛋白质-蛋白质相互作用(PPI)网络，并筛选核心靶点。采用 Metascape 平台对荔枝核治疗胃癌和肝癌的共同靶点进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果筛选得到荔枝核有效化学成分8 个，对应作用靶点179 个，胃癌相关靶点1 177个，肝癌相关靶点1 281 个。荔枝核治疗胃癌、肝癌的共同靶点有61 个，进一步筛选得到核心靶点20 个，包括MYC 原癌基因、雌激素受体1、细胞周期蛋白 D1、表皮生长因子受体等。GO 功能富集分析结果显示，荔枝核治疗胃癌和肝癌涉及的生物过程主要有凋亡信号通路、对无机物质的反应等;涉及的细胞组分主要有膜筏、囊泡腔等;涉及的分子功能主要有激酶结合、DNA 结合转录因子结合等。KEGG 通路富集分析结果显示，荔枝核治疗胃癌和肝癌主要与癌症相关通路、血管内皮生长因子(VEGF)信号通路、缺氧诱导因子1(HIF-1)信号通路有关。结论荔枝核主要通过调节凋亡信号通路等生物过程，作用于膜筏、囊泡腔等细胞组分，进而实现激酶结合、DNA 结合转录因子结合等分子功能，以及调控癌症相关通路、VEGF 信号通路、HIF-1 信号通路等，最终起到防治胃癌和肝癌的作用。【关键词】荔枝核;胃癌;肝癌;异病同治;网络药理学【中图分类号】2855【文献标识码】A【文章编号】0253-4304(2022)23-2764-07DOI:1011675/j issn0253-430420222312Exploration of litchi semen in treating different diseases with the same method forgastric cancer and liver cancer:a mechanism study based on network pharmacologyYIN Shuo-xin1，LU-Xin1，WANG Shu-ping1，LI An-guo1，QIU Xue-zhu1，LI Sheng-chi1，HUANG Hong-xiang1，ZHANG Tao2，CHEN Yuan-neng2(1 Graduate School，Guangxi University of Chinese Medicine，Nanning 530000，Guangxi，China;2 Department ofGastroenterology，uikang Hospital Affiliated to Guangxi University of Chinese Medicine，Nanning 530011，Guangxi，China)【Abstract】ObjectiveTo explore the mechanism of litchi semen in treating different diseases with the samemethod for gastric cancer and liver cancer based on network pharmacology MethodsThe effective chemical componentsand their effect targets of litchi semen were searched from the Traditional Chinese Medicine Systems Pharmacology Databaseand Analysis PlatformThe targets related to gastric cancer and liver cancer were obtained by the databases ofGeneCards and OMIM The common targets were acquired by the intersection of targets related to gastric cancer andliver cancer with effect targets of litchi semen effective chemical components The protein-protein interaction(PPI)networkof common targets were constructed，and the core targets were screen by the STING platform and CytoScape 3 7 2software The Metascape platform was used to perform Gene Ontology(GO)functional enrichment analysis and KyotoEncyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the common targets of litchi semen in thetreatment of gastric cancer and liver cancer esultsEight effective chemical components of litchi semen and 1794672Guangxi Medical Journal，Dec 2022，Vol 44，No 23corresponding effect targets，1177 targets related to gastric cancer，as well as 1281 targets related to liver cancer werescreened There were 61 common targets of litchi semen for treating gastric cancer and liver cancer，and 20 coretargets were obtained through further screening，including MYC proto-oncogene，estrogen receptor 1，cyclin D1 andepidermal growth factor receptor，etc The results of GO functional enrichment analysis revealed that litchi semen fortreating gastric cancer and liver cancer was involved in the biological processes mainly concerning apoptotic signalingpathway，and response to inorganic substance，etc，in the cell composition mainly concerning membrane raft andvesicle cavity，and in the molecular functions mainly concerning kinase binding，DNA-binding transcription factorbinding，etc The results of KEGG pathway enrichment analysis depicted that litchi semen for treating gastric cancerand liver cancer was mainly related to pathways in cancer，vascular endothelial growth factor(VEGF)signalingpathway，hypoxia inducible factor 1(HIF-1)signaling pathway ConclusionLitchi semen mainly regulates biologicalprocesses in terms of apoptosis signaling pathway，etc，acts on cell composition concerning membrane rafts and vesiclecavities，etc，and further realizes molecular functions of kinase binding，DNA binding transcription factor binding，etc，andmodulates pathways in cancer，VEGF signaling pathway and HIF-1 signaling pathway，etc，and finally exerts the effectof prevention and treatment of gastric cancer and liver cancer【Key words】Litchi semen，Gastric cancer，Liver cancer，Treating different diseases with the same method，Network pharmacology胃癌的致病因素复杂，环境和遗传因素都可能对其发生和发展产生影响1。尽管在过去的几十年里，胃癌的新发和死亡病例数均较前减少，但它仍是全球范围内第 5 大常见癌症和第 4 大常见癌症死亡原因1。近年来，肝癌的病死率超过胃癌，已成为全球范围第 3 大癌症死亡原因2。肝癌的发病危险因素主要有病毒性肝炎、酒精性肝病、代谢性肝病和长期接触毒素3。虽然我国对乙肝和丙肝的防控已经使部分地区的肝癌发病率明显降低，但由于人口基数大，每年新确诊的肝癌患者数量仍居高不下4。胃癌和肝癌早期缺乏特异性症状，因此多数患者确诊时常已处于癌症中晚期，常规西医治疗效果欠佳。中医药在癌症的防治中发挥着至关重要的作用，其能提高西药的疗效，且药物副作用小，可改善患者生活质量5 6。此外，中医药还能延缓癌症进展的速度、缓解患者的临床症状，从而提高患者 5 年生存率，如今在胃癌和肝癌治疗中的应用也越来越广泛7。中医理论认为胃癌的形成是在素体脾胃虚寒的基础上，饮食生冷，感受湿热寒邪，日久郁积引起的气血运行不畅8，最常见的证型为脾气虚证、肝胃不和证、痰湿证、热毒证、血虚证、血瘀证等9。胃癌的治疗原则一般以益气健脾、活血化瘀、清热解毒为主10。肝癌的病机以正气不足、痰瘀毒等邪气内盛为主，治疗以扶正祛邪为法11。荔枝核为无患子科、亚热带常绿乔木荔枝的干燥成熟种子，性温，味甘、微苦，