Utilizing network pharmacology and experimental validation to explore the potential molecular mechanisms of raw Pinellia ternate in treating esophageal cancer

利用网络药理学和实验验证探讨生半夏治疗食管癌的潜在分子机制

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作者:Yanxin Liu, Yunfei Bai, Jinbang Zhang, Reginaldo Silva-Filho, Qingchun Zhu, Zhen Lei

Background

Esophageal cancer (EC) is a highly lethal malignancy with a grim prognosis and high mortality rates, primarily treated through surgery and radiotherapy. Herbal remedies are emerging as complementary approaches in cancer therapy. Here, we explore the potential therapeutic benefits of Chinese medicine raw Pinellia ternata (RP) in EC using web-based pharmacological

Conclusions

The pharmacodynamic mechanism of RP in the treatment of esophageal carcinoma was preliminarily revealed, which provided ideas and the basis for further experimental study of RP in the treatment of esophageal carcinoma.

Methods

The chemical components of RP were obtained by data mining via searches of the systematic pharmacology database, analysis platform, and literature on traditional Chinese medicine (TCM). The properties of the main components of RP were calculated using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of the components were mined and collected through multiple databases, and the relevant potential targets of efficacy were imported into Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to obtain protein interactions. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis of the potential targets were performed through Metascape. A target-pathway network was established using Cytoscape, and topological analysis was performed on the network so as to obtain the relevant targets and pathways of RP in the treatment of EC. The inhibitory effect of RP on human EC cells was verified by cell experiments.

Results

Thirteen bioactive components of RP were screened, 87 related targets were obtained by construction, and 68 co-targets were obtained after taking intersection with EC related genes. The results of the protein-protein interaction (PPI) network analysis of the targets showed that the pharmacodynamic targets of hemicellulose might be closely related to the signaling pathways such as PI3K-Akt, FOS/JUN, and HIF-1. Meanwhile, GO and KEGG enrichment analysis showed that PI3K-Akt was also significantly enriched. The in vitro cellular experiments further indicated that raw hemicrania could inhibit EC through the PI3K-Akt signaling pathway. Conclusions: The pharmacodynamic mechanism of RP in the treatment of esophageal carcinoma was preliminarily revealed, which provided ideas and the basis for further experimental study of RP in the treatment of esophageal carcinoma.

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