Uncovering the Mechanism of the Effects of Pien-Tze-Huang on Liver Cancer Using Network Pharmacology and Molecular Docking.

Yan Lou,Shanghui Liu,Run Wang,Jia Liu

doi:10.1155/2020/4863015

Abstract

Pien-Tze-Huang (PTH) has a long history in the treatment of liver cancer. However, its molecular mechanism of action remains unclear. TCMSP and TCM were used to collect the active ingredients. Bioactive compounds targets were predicted by reverse pharmacophore models. The antiliver cancer targets of PTH were selected by gene comparison of liver cancer in the GEO database. Molecular docking was used to verify the binding activity of the targets and the active ingredients. The DAVID was used to analyze the gene function and signal pathway. A model was built with Cytoscape. The core genes were obtained by PPI network. We screened the 4 main medicinal ingredients of PTH to obtain 16 active ingredient, 190 potential targets, and 6 core genes. We found that active small molecules exert anticancer effects by multiple pathways. The core genes were involved in multiple biological processes. We also found that eight chemical components play a greater role in inhibiting liver cancer. PTH achieves the effect of inhibiting liver cancer through the synergistic effect of multiple components, multiple targets, and multiple pathways. This study provides a potential scientific basis for further elucidating the molecular mechanism of action of PTH against liver cancer.

Highlights

Liver cancer is a common clinical malignant tumor of liver. e incidence ranks the 5th in the world [1]. e fatality rate ranks the 2nd in the world [2]
Prediction Results of Bioactive Compounds Targets in PTH for Liver Cancer. rough the PharmMapper, 4505 potential targets were obtained by analysing 16 active ingredients in PTH. e target names were input into UniProt database, and all the target names were corrected to the gene names of the target; 986 target genes were obtained. 307 target genes were obtained after further gene deduplication. en, 307 target genes and 15385 differentially expressed mRNA (DEmRNA) of GEO were intersected, and 197 potential liver cancer related targets were screened by the intersection of Venn (Figure 1)
With 16 active ingredients as ligands and 197 target protein genes as receptors, 614 groups of corresponding relationships were formed. e binding energy of each group can be calculated by molecular docking, and the binding energy of docking results can be displayed by heatmap (Figure 2)

Summary

Introduction

Liver cancer is a common clinical malignant tumor of liver. e incidence ranks the 5th in the world [1]. e fatality rate ranks the 2nd in the world [2]. Many clinical studies have proved that Chinese medicine has good effects in improving the symptoms of patients with advanced liver cancer [5], reducing tumor recurrence [6], and controlling disease progression [7]. Pien-Tze-Huang (PTH), a classic Chinese medicine prescription, is made from Chinese ingredients such as Rhizoma Notoginseng (Sanqi in Chinese), Moschus (Shexiang in Chinese), Calculus Bovis (Niuhuang in Chinese), and Snake Gall (Shedan in Chinese) [8]. It is a proprietary Chinese medicine with the function of detoxification, antiinflammation, and immune regulation [9, 10]. Studies on the effects of PTH on lung cancer [18], intestinal cancer [19, 20], osteosarcoma [21], and liver cancer [22] have been reported, but the active ingredients of PTH on liver cancer and the relevant molecular mechanisms are still unclear

Methods

Results

Conclusion