杠板归抑制小鼠H22肝癌的作用机制  

Inhibitory effect and action mechanism of Polygonum perfoliatum on H22 liver carcinoma in mice

作　　者：周琳 杜金城 杜钢军[1] ZHOU Lin;DU Jincheng;DU Gangjun(Pharmaceutical College of Henan University,Kaifeng 475004,China;College of traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]河南大学药学院药物研究所,河南开封475004 [2]湖南中医药大学中医学院,湖南长沙410208

出　　处：《药物评价研究》2019年第10期1935-1941,共7页Drug Evaluation Research

基　　金：河南省自然科学基金项目（182300410310）

摘　　要：目的观察杠板归对小鼠H22肝癌的抑制作用,分析其可能的作用机制。方法建立H22皮下移植小鼠模型评价杠板归对肿瘤生长的影响;二甲苯诱导的耳肿胀评价杠板归对荷瘤小鼠炎症的影响;网络药理学分析杠板归抗肿瘤和抗炎可能的作用机制。结果杠板归对H22皮下肿瘤生长有明显抑制作用(P<0.05),显著降低二甲苯诱导的荷瘤小鼠耳肿胀(P<0.05)。通过上海有机所化学专业数据库以口服生物利用度(OB)≥30%和类药性(DL)≥0.18筛选杠板归4种有效成分,与生物芯片肝癌上下调基因蛋白分子对接得到106个预测靶点,预测靶点与TTD比对得到13个肝癌治疗靶点。蛋白相互作用网络(PPI)分析STAT3、IL-6、IL-1β、HBG2、TLR4、HBB、HBE1、HBD为8个核心靶点,其参与27个KEGG通路和27个生物过程。结论杠板归对小鼠H22肝癌有抑制作用,能减轻荷瘤小鼠炎症,其作用与4个活性成分参与"泛素化介导蛋白水解"、"核因子(NF)-κB信号传导"、"Janus激酶-信号转导与转录激活子(JAK-STAT)信号传导"等通路有关。Objective To observe the inhibitory effect of Polygonum perfoliatum L. on H22 liver carcinoma in mice and explore its possible action mechanisms. Methods Effect of Polygonum perfoliatum L. on tumor growth was evaluated using H22 subcutaneously transplanted tumor model in mice, effect of Polygonum perfoliatum L on inflammation was examined by ear edema in tumor bearing mice. Network pharmacology was used to analyze the possible action mechanisms by which Polygonum perfoliatum L. exerts anti-tumor and anti-inflammation efficacy. Results Polygonum perfoliatum L. had an anti-tumor effect on H22 liver carcinoma in mice and obviously decreased xylene-induced ear edema in tumor-bearing mice(P < 0.05). 4 active components with OB ≥ 30%and DL ≥ 0.18 in Shanghai Institute of Organic Chemistry database, and up-and-down genes of liver cancer in the biochip were selected for molecular docking. 106 predicted targets were compared to liver cancer therapeutic targets in TTD, there were 13 liver cancer therapeutic targets related with four active components. PPI analysis indicates that STAT3, IL6, IL1 B, HBG2,TLR4, HBB, HBE1, HBD are 8 core targets which involve in 27 KEGG(Kyoto Encyclopedia of Genes and Genomes) pathways and27 GO(gene ontology) biological process. Conclusion Polygonum perfoliatum L. has an inhibitory effect on H22 liver cancer and could decrease inflammation in tumor bearing mice, its action mechanisms are associated 4 active components which involve in "ubiquitination-mediated proteolysis", "NF-κB signaling", and "JAK-STAT signaling", et al pathway.

关 键 词：杠板归 肝癌 炎症 网络药理学 JAK-STAT信号传导 

分 类 号：R944[医药卫生—药剂学]