Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology

Abstract

Background: Ginseng, a traditional Chinese medicine, was used to prevent and treat many diseases such as diabetes, inflammation, and cancer. In recent years, there are some reports about the treatment of lung adenocarcinoma with ginseng monomer compounds, but there is no systematic study on the related core targets and mechanism of ginseng in the treatment of lung adenocarcinoma up to now. Therefore, this study systematically and comprehensively studied the molecular mechanism of ginseng in the treatment of lung adenocarcinoma based on network pharmacology and further proved the potential targets by A549 cell experiments for the first time.

Methods: The targets of disease and drug were obtained from Gene database. Subsequently, the compound-target network was constructed, and the core potential targets were screened out by plug-in into Cytoscape. Furthermore, the core targets and mechanism of ginseng in the treatment of lung adenocarcinoma were verified by MTT test, cell scratch test, immunohistochemistry, and qRT-PCR.

Results: 1791 disease targets and 144 drug targets were obtained by searching the Gene database. Meanwhile, 15 core targets were screened out: JUN, MAPK8, PTGS2, CASP3, VEGFA, MMP9, AKT1, TNF, FN1, FOS, MMP782, IL-1β, IL-2, ICAM1, and HMOX1. The results of cell experiments indicate that ginseng could treat lung adenocarcinoma by cell proliferation, migration, and apoptosis. In addition, according to the results of the 15 core targets by qRT-PCR, JUN, IL-1β, IL-2, ICAM1, HMOX1, MMP9, and MMP2 are upregulated core targets, while PTGS2 and TNF are downregulated core targets.

Conclusion: This study systematically and comprehensively studied 15 core targets by network pharmacology for the first time. Subsequently, it is verified that 9 core targets for ginseng treatment of lung adenocarcinoma, namely, JUN, IL-1β, IL-2, ICAM1, HMOX1, MMP9, MMP2, PTGS2, and TNF, are closely related to the proliferation, migration, and apoptosis of lung adenocarcinoma cells. This study has reference value for the clinical application of ginseng in the treatment of lung adenocarcinoma.

Figure 1

Network relationship of key targets and active compounds of ginseng. Green represents the active compounds of ginseng, red represents lung adenocarcinoma genes, and yellow represents non-lung adenocarcinoma genes.

Figure 2

The functional analysis for identified compounds-related targets. The docking targets-related GO terms.

Figure 3

Functional analysis for identified compounds-related targets. The docking targets-related KEGG pathways distribution.

Figure 4

The effect of ginseng on the proliferation and apoptosis of lung adenocarcinoma. (a) MTT test result (control group, cyclophosphamide group, ginsenoside group, polysaccharide group) (^∗p < 0.05, ^∗∗p < 0.01). (b) Immunocytochemistry result of apoptosis factor (10×, 20×, 40×).

Figure 5

The effect of ginseng on the migration of lung adenocarcinoma cells (0 h, 6 h, 24 h).

Figure 6

The mRNA expression levels of 15 core targets. Compared with the control group, the expression levels of JUN, IL-1β, IL-2, ICAM1, HMOX1, MMP9, MMP2, PTGS2, and TNF mRNA in the administration group have significant difference in the treatment group (^∗p < 0.05, ^∗∗p < 0.01).