Network-Based Pharmacology and in Vitro Experiments Validate that Cepharanthine Inhibit Bladder Cancer Cell Migration, Invasion and Emt Progression Via the Rap1 Signaling Pathway

• DOI: 10.2139/ssrn.4548494
• Publication Date: 2023-08-31T16:00:32Z
• Authors: Bo Chen; Lin Chen; Wenbin Dai; Xin Zhou; Xiaoming Long; Yao Shu; Song Wang; Jun Long; Jinbang Wu; Bo Wu; Dianxiang Lu; Jin Yang
• Keywords: Rap1; Systems pharmacology

Ethnopharmacological revelvance: Cepharanthine is one of the main active components medicinal plant Stephania japonica (Thunb.) Miers, which has obvious anti-tumor activities. However, anti-bladder cancer effect cepharanthine not been reported.Objective: The potential targets and signaling pathways against bladder were predicted by network pharmacological screening, its molecular mechanism was verified cellular experiments in vitro.Materials methods: pharmacology approach used to screen possible cancer. anti-proliferation on HT1376 5637 cells observed CCK-8 colony formation experiment. migration invasion ability wound healing test trans-well assay. proteins expression related RAP1 pathway, cell migration, Epithelial-Mesenchymal Transition (EMT) detected using western blotting.Results: 313 cepharanthine-acting targets, 277 candidate disease cancer, 22 intersecting 12 core screened from Swiss Target Prediction database, Pharm Mapper database GeneCards database. pathway KEGG enrichment analysis. In vitro showed that inhibited proliferation, cells. activated upregulating EPAC1 downregulating E-cadherin C3G protein through regulation these two pathways, promoted form, GTP protein, reduced downstream proteins, PKD1 ITGA5. After activation invasion-related MMP2, MMP9 EMT-related N-cadherin Snail less. we found our results Vimentin affected.Conclusion: able inhibits EMT process activating pathway.