天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (5): 868-880.doi: 10.16333/j.1001-6880.2024.5.016

• 数据研究 • 上一篇    下一篇

基于整合药理学和实验验证探讨健脾除痰解毒方干预肺癌的作用机制

詹雪1,冯诗函1,杨   倩1,谭   琪1,夏琳涛1,张佳艳1,范宇翔2,王淑美1*   

  1. 1重庆医科大学中医药学院 中医药防治代谢性疾病重庆市重点实验室,重庆 400016;2南京中医药大学第一临床医学院,南京 210023
  • 出版日期:2024-05-28 发布日期:2024-05-29
  • 基金资助:
    国家中医药管理局课题(JDZX2015073);重庆市自然科学基金面上项目(CSTB2022NSCQ-MSX1564)

Intervention mechanism of Jianpi Chutan Jiedu Decoction on lung cancer based on integrated pharmacology and experimental validation

ZHAN Xue1,FENG Shi-han1,YANG Qi1,TAN Qi1,XIA Lin-tao1,ZHANG Jia-yan1,FAN Yu-xiang2,WANG Shu-mei1*   

  1. 1Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases,College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400010,China;2First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China
  • Online:2024-05-28 Published:2024-05-29

摘要:

基于整合药理学和实验验证探讨健脾除痰解毒方(Jianpi Chutan Jiedu Decoction,JCJD)干预肺癌的作用机制。采用中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)V2.0,检索并获取健脾除痰解毒方靶标及功能信息,以及肺癌疾病靶标及功能信息,借助中医关联网络挖掘平台构建“疾病-方剂”关联网络,并通过网络拓扑特征计算、自定义多维关联网络可视化(方剂-中药材-核心靶标-通路-疾病)以及基因本体(GO)功能和依托Reactome数据库的Pathway信息进行富集分析,发现健脾除痰解毒方干预肺癌的关键网络靶标及其作用机制。最后通过动物实验进一步验证整合药理学结果。结果共获得健脾除痰解毒方干预肺癌的核心靶标53个;GO富集分析得到生物过程有20种条目,细胞组分有11种条目,分子功能有20种条目;Reactome Pathway富集分析得到11个条目,主要涉及呼吸电子传递、TP53调节代谢基因、细胞内受体的SUMO化、白细胞介素(IL)-4和IL-13通路等信号通路。动物实验结果显示与模型组比较,联合组肿瘤组织中乳酸含量明显下降(P<0.05),联合组可明显上调肿瘤组织中磷酸酯酶与张力蛋白同源物(PTEN)蛋白平均光密度值(P<0.05),降低丙酮酸激酶M2(PKM2)和己糖激酶2(HK2)蛋白平均光密度值(P<0.05);与模型组比较,联合组可明显上调肿瘤组织中肿瘤抑制蛋白(P53)、PTEN mRNA及蛋白表达(P<0.01,P<0.05),降低肿瘤组织中TP53诱导的糖酵解与凋亡调控因子(TIGAR)、葡萄糖转运蛋白1 (GLUT1)、PKM2、HK2 mRNA及蛋白表达(P<0.01)。综上,健脾除痰解毒方通过TP53调节代谢基因来下调葡萄糖代谢,从而抑制肺癌增殖。

关键词: 整合药理学, 实验验证, 健脾除痰解毒方, 肺癌, TP53, 代谢

Abstract:

To explore the mechanism of Jianpi Chutan Jiedu Decoction (JCJD) on lung cancer based on integrated pharmacology and experimental verification.The integrated pharmacology based research platform of traditional Chinese medicine (TCMIP) v2.0 was used to retrieve and obtain the target and function information of JCJD and lung cancer disease target and function information.The "disease prescription" association network was constructed with the help of the Chinese Medicine Association Network mining platform,and the network topology characteristics were calculated The user-defined multidimensional correlation network visualization (prescription-Chinese herbal medicine-core target-pathway-disease),gene ontology (GO) function and the path information based on the reactome database were enriched and analyzed,and the key network targets and mechanism of action of JCJD for lung cancer were found.Finally,the results of integrated pharmacology were further verified by animal experiments.A total of 53 core targets of JCJD for lung cancer were obtained;GO enrichment analysis revealed the presence of 20 items in biological processes,11 items in cellular components,and 20 items in molecular functions;11 items were obtained from the enrichment analysis of react pathway,mainly involving respiratory electron transport,TP53 regulates metabolic genes,SUMOylation of intracellular receptors,interleukin-4 and interleukin-13 pathways and other signaling pathways.The results of animal experiments showed that compared with the model group,the content of lactic acid in tumor tissue in the combined group was significantly decreased (P<0.05).The combined group could significantly increase the average optical density of phosphatase and tensin homolog (PTEN) protein in tumor tissue (P<0.05),and reduce the average optical density of pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) protein (P<0.05);Compared with the model group,the combined group could significantly increase the expression of tumor suppressor protein (P53),PTEN mRNA and protein in tumor tissues (P<0.01,P<0.05),and reduce the expression of TP53 induced glycolysis and apoptosis regulator (TIGAR),glucose transporter 1 (GLUT1),PKM2,HK2 mRNA and protein in tumor tissues (P<0.01).In conclusion,JCJD can down regulate glucose metabolism by regulating metabolic genes through TP53,thereby inhibiting the proliferation of lung cancer.

Key words: integrated pharmacology, experimental validation, Jianpi Chutan Jiedu Decoction, lung cancer, TP53, metabolism

中图分类号:  R285.5