Distribution Mechanism of Network Modules in Combined Treatment of Liver Cancer with Jiuwei Zhengxiao Granules
10.13422/j.cnki.syfjx.20220817
- VernacularTitle:九味癥消颗粒配伍治疗肝癌的网络模块分布机制分析
- Author:
Rong LI
1
;
Hao GU
1
;
Pengqian WANG
2
;
Xuewu LIU
3
;
Dongdong PENG
3
;
Dejian JIANG
3
;
Bo WANG
1
;
Jun LIU
1
;
Zhong WANG
1
Author Information
1. Institute of Basic Research in Clinical Medicine，China Academy of Chinese Medical Sciences，Beijing 100700，China
2. Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
3. Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs， Hunan Prima Drug Research Center Co. Ltd.， Changsha 410331，China
- Publication Type:Journal Article
- Keywords:
Jiuweizhengxiao granules;
liver cancer;
modular pharmacology;
main module;
pharmacological mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(15):162-172
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules （JWZX） based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology，the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study，the average degree （AD） of the nodes in the modules was used as an index to screen the main modules of the disease，and the intervention of the sovereign drugs，minister drugs，and assistant drugs on the main modules was explored. Finally，the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment，JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor （P<0.05，P<0.01）. The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor （TNF），epidermal growth factor receptor （EGFR），vascular endothelial growth factor A （VEGFA），transcription factor （JUN），tumor protein p53 （TP53），and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8，and the minister drugs such as Centipeda Herba jointly intervened in modules 1，3，5，8，10，and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3，5，10，and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules，and the pathway functions involved 12 categories including cancer，signal transduction，immune system，endocrine system，and amino acid metabolism. The functions of the four major modules involved cancer，signal transduction，and immune system. According to the results of literature verification，the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） and hypoxia-inducible factor-1 （HIF-1） signaling pathways，reduction of the immunosuppressive effect in the tumor microenvironment，and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer，and the therapeutic efficacy was achieved through the multiple targets，multiple modules，and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer，which provides a new idea for interpreting the complex mechanism of prescription compatibility.
