基于分子动力学模拟和实验评价探讨黄芪甲苷对HepG2细胞的作用机制

目的 基于分子动力学模拟和实验评价揭示黄芪甲苷对HepG2细胞的作用机制。方法 构建“药物-疾病”网络药理图，分析黄芪甲苷（AS-IV）作用于肝细胞癌（HCC）的核心基因，筛选关键信号通路，建立“药物-靶点”分子动力学模型；体外实验检测HepG2细胞迁移、增殖、侵袭能力；流式细胞术检测HepG2细胞周期及凋亡；qRT-PCR检测核心基因相对表达量。结果 AS-IV作用于HCC核心靶点为VEGFA；体外实验结果显示：与对照组比较，高浓度AS-IV对HepG2细胞的迁移、侵袭和增殖活力具有抑制作用，能阻滞HepG2细胞从G1期向G2期转移，促进其凋亡，可下调VEGFA mRNA表达，上调TGF-β1 mRNA表达。结论 AS-IV可能通过多靶点、多通路抑制肝癌细胞的增殖。

Mechanism of Astragaloside IV on HepG2 Cells Based on Molecular Dynamics Simulation and Experimental Evaluation

Objective To reveal the mechanism of action of AS-IV on HepG2 cells based on molecular dynamics simulation and experimental evaluation. Methods We constructed a “drug-disease” network pharmacological map, analyzed the core genes of astragaloside IV (AS-IV) in HCC, screened key signaling pathways, and established a “drug-target” molecular dynamics model. In vitro assay was used to detect migration, proliferation and invasion abilities. Flow cytometry and qRT-PCR were used to detect the effect of AS-IV on the cell cycle and apoptosis, and the expression of core gene of HepG2. Results The core target of AS-IV acting on HCC was VEGFA. Compared with the control group, the high concentration of ASIV significantly inhibited the migration, invasion and proliferation of HepG2 cells, blocked the metastasis of HepG2 cells from G1 to G2 phase, promoted their apoptosis, down-regulated VEGFA expression and upregulated TGF-β1 expression. Conclusion AS-IV may inhibit the proliferation of hepatocellular carcinoma cells through multi-target and multi-pathway.