Mechanism of Compound Kushen Injection in the Treatment of Acute Myeloid Leukemia from the Analysis Perspectives

被引:0
|
作者
Zeng, Jia [1 ]
Tian, Huiqun [2 ]
Kang, Le [3 ]
Wu, Qian [1 ]
Liu, Shiwen [1 ]
Xiao, Yugang [1 ]
Shao, Hongwei [4 ]
Huang, Guangrui [5 ]
Liu, Song [1 ,4 ,6 ,7 ]
机构
[1] Guangdong Pharmaceut Univ, Sch Pharm & Clin Pharm, Sch Integrat Pharm, Guangzhou 510006, Peoples R China
[2] China Three Gorges Univ, Peoples Hosp 2, Yichang, Peoples R China
[3] Wenzhou Med Univ, Dept Biomed Sci Lab, Affiliated Dongyang Hosp, Dongyang 322100, Peoples R China
[4] Guangdong Pharmaceut Univ, Guangdong Prov Key Lab Biotechnol Drug Candidates, Guangzhou 510006, Peoples R China
[5] Beijing Univ Chinese Med, Sch Life Sci, Beijing 100029, Peoples R China
[6] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Key Specialty Clin Pharm, Guangzhou 510080, Peoples R China
[7] Guangdong Pharmaceut Univ, Guangdong Prov Key Lab Adv Drug Delivery Syst, Guangzhou 510006, Guangdong, Peoples R China
关键词
Acute myeloid leukemia; compound kushen injection; network pharmacology; molecular dynamics; molecular docking; PPI; THERAPEUTIC TARGET; PI3K INHIBITOR; CELLS; OPTIMIZATION; TYROSINASE; APOPTOSIS; EFFICIENT; ACCURACY; NETWORK; ERBB2;
D O I
10.2174/0115733947271076231204181500
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Chemotherapy resistance often occurs in the conventional treatment with AML and results in poor cure rates. CKI was found to have a good therapeutic effect when it was combined with other chemotherapy drugs in the clinical treatment of AML. However, the underlying mechanism is unclear. Therefore, this study aims to preliminarily describe the pharmacological activity and mechanism of CKI through comprehensive network pharmacology methods.Objective This study aimed to explore the possible mechanism of Compound Kushen Injection (CKI) in the treatment of acute myeloid leukemia (AML) by using network pharmacology, molecular docking, and molecular dynamics techniques.Methods Active compounds of CKI were identified based on the Traditional Chinese Medicine Systems Pharmacy (TCMSP) database, and the related targets of the active compounds were predicted using Swiss Target Prediction; AML-related targets from Gene Cards and Online Mendelian Inheritance in Man (OMIM) were collected. Protein-protein interaction (PPI) network was constructed, and its mechanism was predicted through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The protein-protein interaction (PPI) network construction, module partitioning, and hub node screening were visualized by using the Cytoscape software and its plugins. These module partitionings were also verified by using molecular docking and molecular dynamics modeling.Results Fifty-six active ingredients corresponding to 223 potential targets were identified. Biological function analysis showed that 731, 70, and 137 GO entries were associated with biological processes, cellular components, and molecular functions, respectively. A total of 163 KEGG pathways were identified. Network analysis showed that the key anti-AML targets of CKI are MAPK3, EGFR, SRC, PIK3CA, and PIK3R1 targets, which are involved in the PI3K/Akt and Ras/MAPK signaling pathways or related crosstalk pathways.Conclusion Our results suggested that the key anti-AML targets of CKI, such as MAPK3, EGFR, SRC, PIK3CA and PIK3R1, are involved in the PI3K/Akt and Ras/MAPK signaling pathways or related crosstalk pathways. Concentrating on the dynamic and complex crosstalk regulation between PI3K/Akt and Ras/MAPK signal pathways and related signal pathways may be a new direction in anti-AML therapy in the future.
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收藏
页码:95 / 109
页数:15
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