黄芪注射液治疗宫颈癌的机制研究  

Study on the Mechanism of Huangqi Injection in Treating Cervical Cancer

作　　者：范静 陈立锋[2] 范凌[3] 倪广林[3] 李琦[3] 徐静 佟长青[3] 张灵[3] 张斌[3] Fan Jing;Chen Lifeng;Fan Ling;Ni Guanglin;Li Qi;Xu Jing;Tong Changqing;Zhang Ling;Zhang Bin(Department of Obstetrics and Gymecology,Zhangjiakou Maternal and Child Health Hospital,Zhangjiakou O75000,China;Department of Pathophysiology,Basic Medical College of Hebei North University,Zhangjiakou 075000,China;Hematology Department,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]张家口市妇幼保健院妇产科,河北张家口075000 [2]河北北方学院基础医学院生理教研室,河北张家口075000 [3]河北北方学院附属第一医院血液内科,河北张家口075000

出　　处：《南开大学学报（自然科学版）》2023年第3期61-69,共9页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：Supported by Medical Science Research Projects in Hebei Province(20200508);Zhangjiakou Municipal Science and Technology Plan(2221185D)。

摘　　要：宫颈癌是一种常见的妇科恶性肿瘤,由人乳头瘤病毒(HPV)感染所致.黄芪可以增强细胞和体液免疫功能,抑制肿瘤的生长.黄芪是治疗宫颈癌的潜在选择,可以提高疗效并降低化疗毒性.然而,作用机制仍不明确.本研究采用网络药理学和分子对接技术,GEPIA分析和体外实验探讨黄芪治疗宫颈癌的潜在分子机制.结果表明,从黄芪中筛选出20个活性化合物和180个潜在靶点.通过在线数据库,得到9562个与宫颈癌相关的靶点,获得166个黄芪与宫颈癌共同的靶点.在药物-活性成分-靶点-疾病网络中,槲皮素、山奈酚、芒柄花黄素和异鼠李素是重要的活性成分.在PPI网络中,MAPK1、AKT1、CCND1、FOS、JUN、MAPK14、RELA、HIF1A、IL-2、MYC和ESR1是核心靶点.通过GEPIA分析,ESR1在肿瘤组织中的表达显著低于正常对照组织.GO和KEGG分析表明,黄芪治疗宫颈癌的主要途径涉及TNF、MAPK和PI3K-Akt信号通路.在分子对接中,黄芪4个重要的活性化合物与ESR1分别具有良好的亲和力.最后,MTT实验显示槲皮素、山奈酚、芒柄花黄素和异鼠李素可以抑制HeLa细胞的增殖.qPCR分析显示,槲皮素组、山奈酚组、异鼠李素组和芒柄花黄素组的m RNA表达显著s升高,呈剂量依赖性.在本研究中,黄芪注射液可以抑制HeLa细胞的增殖.具体机制是黄芪注射液中的活性成分,如槲皮素、山奈酚、芒柄花黄素和异鼠李素,可以作用于ESR1等多个靶点和多条信号通路.Cervical cancer(CC)is a common malignant gynecologic tumor that is infected by the human papillomavirus(HPV).Astragalus also known as Huangqi in Chinese can enhance curative efficacy and reduce chemotherapy toxicity for cervical cancer.However,the action mechanism remains unclear.The network pharmacology,molecular docking,GEPIA,and in vitro experiments were used to explore the underlying molecular mechanism of Huangqi in treating CC.Results showed that a total of 20 active compounds and 180 potential targets of Huangqi were chosen.In an drug-active component-target-disease network,quercetin,kaempferol,formononetin,and isorhamnetin were the important active components.In PPI network,MAPK1,AKT1,CCND1,FOS,JUN,MAPK14,RELA,HIF1A,IL-2,MYC,and ESR1 were the core targets.The expression of ESR1 was significantly lower in tumor tissues than in normal control tissues by GEPIA analysis.KEGG analyses showed that the main pathways of Huangqi in treating CC involved TNF,MAPK,and PI3K-Akt signaling pathways.In molecular docking,the active compounds of Huangqi had a good affinity with ESR1.Finally,the MTT assay and qPCR analysis validated the therapeutic effect of the active ingredients of Huangqi injection on cervical cancer.

关 键 词：黄芪注射液 宫颈癌 ESR1 网络药理 分子对接 机制 

分 类 号：R737.33[医药卫生—肿瘤]