摘要
目的探析瑞香狼毒活性成分治疗晚期肝细胞癌的分子机制。方法首先通过检索中药系统药理数据库和分析平台(TCMSP)筛选瑞香狼毒中的活性成分及其对应的靶蛋白分子,通过IPA软件数据库筛选晚期肝细胞癌相关分子。利用软件网络分析功能分别构建靶蛋白分子和晚期肝细胞癌相关分子的分子网络。通过软件比较功能,分析二者共同作用的生物学通路及作用位点。结果从中药瑞香狼毒中筛选出4个活性成分,其对应的靶蛋白共18个,从IPA软件中选出晚期肝细胞癌相关基因共40个。前者主要的分子网络功能是与组织损伤、机体异常及心血管疾病相关,后者的分子网络功能主要与癌症、消化道疾病及肝脏疾病相关分子有关,且各自有不同的信号通路富集。对比前5位共有的信号转导通路,发现PI3K/AKT信号通路是共有的重要信号通路之一。PI3KCG、HSP90、PTGS2是瑞香狼毒活性靶蛋白中调控PI3K/AKT信号通路的作用分子。结论本研究推测瑞香狼毒可能通过PI3KCG、HSP90、PTGS2调控PI3K/AKT信号通路,来抑制肿瘤血管生成,发挥抗肿瘤作用。
Objective To explore the molecular mechanism of the active ingredients of Stellera chamaejasme L.in treatment of advanced hepatocellular carcinoma.Methods Firstly,active ingredients and corresponding target proteins in Stellera chamaejasme L.were screened from TCMSP website,and related molecules in advanced hepatocellular carcinoma were screened from IPA software database.The molecular networks of target proteins and advanced hepatocellular carcinoma related molecules were constructed by software network analysis function.By the compare functions of the software,the biological pathways and action sites of target proteins and related molecules were analyzed.Results Four active ingredients were screened from Stellera chamaejasme L.,and 18 target proteins were identified.A total of 40 molecules related to advanced hepatocellular carcinoma were selected from IPA software.The main molecular network functions of the target proteins were related to tissue damage,body abnormalities and cardiovascular diseases,while the advanced hepatocellular carcinoma related molecules were mainly related to cancer,digestive tract diseases and liver diseases.The molecules in each network were enriched to different signal pathways.Comparing the top five common signal transduction pathways,we found that PI3 K/AKT signaling pathway was one of the most important signaling pathways.PI3 KCG,HSP90 and PTGS2 were the active target proteins of Stellera chamaejasme L.,which regulated the PI3 K/AKT signaling pathway.Conclusion This study suggests that Stellera chamaejasme L.can inhibit angiogenesis and play an anti-tumor role through regulate the PI3 K/AKT signaling pathway by PI3 KCG,HSP90 and PTGS2.
作者
魏飞力
吴梦丽
郭丽
谢棒祥
杜宇琼
陈德喜
刘晓霓
Wei Feili;Wu Mengli;Guo li;Xie Bangxiang;Du Yuqiong;Chen Dexi;Liu Xiaoni(Beijing Center of Precision Medical and Transformational Engineering for Hepatitis and Hepatocellular Carcinoma,Beijing Institute of Hepatology,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China;School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2020年第4期1004-1010,共7页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
北京市肝病研究所所内基金(Y-2019-3PT):晚期肝细胞癌相关分子网络机制研究(核酸测序平台项目),负责人:魏飞力
国家科技部“重大新药创制”科技重大专项(2013ZX09301307001004):瑞香狼毒抗肿瘤中药制剂新药研究,子任务负责人:刘晓霓
关键词
网络药理学
瑞香狼毒
晚期肝细胞癌
分子机制
IPA
Network pharmacology
stellera chamaejasme L.
advanced hepatocellular carcinoma
molecular mechanism
IPA
作者简介
通讯作者:陈德喜,教授,博士生导师,主要研究方向:肝癌分子机制;通讯作者:刘晓霓,研究员,主要研究方向:中药抗肿瘤药理学研究。
