Exploration of the Mechanism of Erzhi Wan in the Treatment of Multiple Myeloma Based on Network Pharmacology,Molecular Docking and Cell Experimental Verification
10.13359/j.cnki.gzxbtcm.2024.08.031
- VernacularTitle:基于网络药理学、分子对接及细胞实验验证探讨二至丸治疗多发性骨髓瘤的作用机制
- Author:
Meng-Dan SHAN
1
;
Ying-Bin ZHONG
;
Man LUO
;
Ming-Feng XIAO
Author Information
1. 广州中医药大学第一附属医院,广东广州 510405
- Keywords:
Erzhi Wan;
multiple myeloma;
network pharmacology;
molecular docking;
Akt/GSK-3β/CCND1/c-Myc pathway;
RPMI-8226 cells
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2024;41(8):2153-2161
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the potential mechanism of Erzhi Wan in the treatment of multiple myeloma(MM)based on network pharmacology,molecular docking and cell experimental verification.Methods Network pharmacology and molecular docking were used to screen the key indicators of drugs-diseases-targets-pathways.MM line RPMI-8226 cells were cultured and given Erzhi Wan intervention.Apoptosis was detected by Annexin V-fluorescein isothiocyanate(FITC)staining.Transwell assay was used to determine cell invasion ability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of protein kinase B(Akt),cyclin D1(CCND1),glycogen synthase kinase 3β(GSK-3β)and c-Myc.Western Blot was used to detect the protein expressions of Akt,phosphorylated protein kinase B(p-Akt),CCND1,c-Myc,GSK-3β and phosphorylated glycogen synthase kinase 3β(p-GSK-3β).Results Fourteen effective components of Erzhi Wan were obtained.There were 142 targets involved in the treatment of MM by Erzhi Wan.The results of pathway enrichment analysis showed that the key targets may be mainly concentrated in cancer pathways,lipids and atherosclerosis.Molecular docking results showed that luteolin and quercetin had good binding activity and stability with GSK-3β.Further cell experimental verification showed that compared with the blank group,the apoptosis rate of cells in the low-,medium-and high-dose groups of Erzhi Wan was significantly increased,the number of cell invasion was decreased,the mRNA and protein levels of GSK-3β were significantly increased,and the mRNA and protein levels of CCND1,Akt and c-Myc were significantly decreased in a dose-dependent manner,among them,the differences in the medium-and high-dose groups being statistically significant(P＜0.05 or P＜0.01).Conclusion The therapeutic effect of Erzhi Wan on MM may be achieved by promoting the expression of GSK-3β and inhibiting the Akt/GSK-3β/CCND1/c-Myc signaling pathway through key active components such as luteolin and quercetin.
