Exploring the Mechanism of Periplogenin in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Biology

Abstract

Lung cancer (the 5-year survival rate is only about 16%) has a low survival rate, and more-effective drugs are urgently needed. Our team discovered that cortex Periplocae Radicis has obvious toxic effects on various cancer cells, including lung cancer cells. However, the mechanism is not clear. Therefore, we used the PubChem database to obtain periplogenin as the target of therapeutic drugs and the TCGA database to obtain differential genes of lung cancer. The results showed that MMP9, PPARG, BMP2, and TGFB2 were the core proteins of periplogenin acting on lung adenocarcinoma (LUAD), and MMP9, angiotensin-converting enzyme (ACE), BMP2, PPARG, MMP13, MMP3, and TGFB2 were the core proteins of periplogenin acting on lung squamous cell carcinoma (LUCS). Through gene ontology (GO) enrichment analysis, it was found that periplogenin mainly acted on LUAD via fatty acid binding, metallopeptidase activity, and monocarboxylic acid binding, and mainly acted on lung squamous carcinoma (LUSC) via endopeptidase activity, metallopeptidase activity, and serine-type peptidase activity. Kyoto Encyclopedia of Genes, and Genomes (KEGG) analysis revealed that the IL-17 signaling pathway, fluid shear stress, atherosclerosis, hepatocellular carcinoma, and so on, were the main signaling pathways of periplogenin acting on LUSC, whereas glycolysis/gluconeogenesis, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were major signaling pathways of periplogenin acting on LUAD. This shows that treatment of lung cancer can be achieved through multi-targeted, and multi-channel periplogenin activity.