Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics.

Abstract

Background and purpose: Gastric cancer is a kind of malignant tumor with high incidence and high mortality, which has strong tumor heterogeneity. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on gastric cancer cells. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, we aimed to reveal the mechanism of PT in treating gastric cancer cells through metabolomic analysis and network pharmacology.

Methods: Metabolomic analysis of two strains of gastric cancer cells treated with the Pinellia ternata extract (PTE) was used to identify differential metabolites, and the metabolic pathways were enriched by MetaboAnalyst. Then, network pharmacology was applied to dig out the potential targets against gastric cancer cells induced by PTE. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape.

Results: The PTE was confirmed to significantly inhibit cell proliferation, migration, and invasion of HGC-27 and BGC-823 cells. The results of cellular metabolomics showed that 61 metabolites were differently expressed in gastric cancer cells of the experimental and control groups. Through pathway enrichment analysis, 16 metabolites were found to be involved in the glycerophospholipid metabolism, purine metabolism, sphingolipid metabolism, and tryptophan metabolism. Combined with network pharmacology, seven bioactive compounds were found in PT, and the networks of bioactive compound-target gene-metabolic enzyme-metabolite interactions were constructed.

Conclusions: In conclusion, this study revealed the complicated mechanisms of PT against gastric cancer. Our work provides a novel paradigm to identify the potential mechanisms of pharmacological effects derived from a natural compound.