Therapeutic Targets of Bufalin on Renal Carcinoma and Mechanisms: Experimental Validation of Network Pharmacology Analysis

Abstract

The possible targets underlying the activity of bufalin on renal cell carcinoma (RCC) were investigated using network pharmacology and experimental approaches. PharmMapper and other databases were explored for predicting the bufalin targets and RCC-related targets. Finally, the enriched pathways and the targets were analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Furthermore, in vitro cell experiments were used to verify bufalin activation of AKT and MAPK signaling pathways in human mesangial cells. The therapeutic targets related to bufalin were identified via 35 intersecting targets. GO analysis identified 29 molecular functions, 16 cellular components, and 91 biological processes. KEGG pathway annotation identified 15 signal transduction pathways and 4 tumor-related pathways.

Bufalin inhibits epithelial-mesenchymal transition and increases radiosensitivity of non-small cell lung cancer via inhibition of the Src signaling

“…The protein concentrations were determined using a bicinchoninic acid (BCA) assay kit (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Equal amounts (20–25 µg) of protein lysate were then resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transferred to polyvinylidene fluoride (PVDF) membranes (Millipore, Burlington, MA, USA), and immunoblotted as formerly described ( 15 ).…”

“…Its structure is similar to digitalis toxin (10)(11)(12). Some studies have demonstrated that bufalin exerts significant anti-tumor activity by inhibiting cell proliferation and angiogenesis and inducing programmed cell death (13)(14)(15). More recently, studies have discovered that bufalin can inhibit the invasion and metastasis of hepatocellular carcinoma by regulating the PI3K/Akt/Mtor/HIF-1α axis (16,17).…”