In this study, we investigated the effect and mechanism of Resibufogenin on renal cell carcinoma based on network pharmacology, molecular docking, and in vitro experiments. The results showed that there were 35 cross-targets between Resibufogenin and renal cell carcinoma. GO and KEGG pathway analyses indicated that Resibufogenin inhibited renal cancer cells through the vascular smooth muscle contraction signalling pathway and EGFR tyrosine kinase inhibitor resistance signaling pathway, and MAPK1, PRKCB, and Resibufogenin had strong associative activities. After different concentrations of Resibufogenin were applied to human renal cancer cells, it was found that the IC50 value was 408.2 nM, 10 nM resibufogenin could significantly inhibit cell migration (p < 0.0001), the percentage of apoptosis and necrosis increased dose-dependently, and the expression of genes of MAPK1 and PRKCB in the cells was significantly reduced (p < 0.001) in a dose-dependent manner. The above results indicate that Resibufogenin can inhibit human renal cell carcinoma through multi-targets and multi-methods, which provides a theoretical basis for the application of Resibufogenin in the treatment of renal cell carcinoma and the development of novel drugs in the future.
Keywords: Resibufogenin; network pharmacology; renal cell carcinoma.