Cordycepin inhibits cell proliferation, metastasis and aerobic glycolysis of gallbladder cancer by inactivating TOP2A-related pathway

Traditional Chinese Medicines have been reported to exert anti-tumor effects and provide novel therapeutic clues for cancer therapy. The present study aims to explore the regulatory mechanism and functions involving cordycepin in gallbladder cancer (GBC), which is hoped to promote its clinical transition. Colony formation, wound healing, and invasion assays were used to assess the abilities of proliferation, migration, and invasion of treated GBC cells, and the apoptotic rates were evaluated by flow cytometry. The glucose uptake ability and lactate production level were tested by corresponding kit accordingly. The data set GSE139682 from the gene expression omnibus database and the websites of GeneCards and Super-PRED were used to predict the potential genes that were influenced by cordycepin in GBC. The interaction between cordycepin and TOP2A was predicted by computational docking simulation. Reverse-transcription quantitative PCR and western blot were used to quantify the levels of target genes. Cordycepin reduced cell proliferation, migration, and invasion and facilitated cell apoptosis in GBC cells in a dosage-dependent manner. Besides, GBC cells treated with cordycepin exhibited lower abilities of glucose uptake and lactate production. Bioinformatics analysis showed that TOP2A might be a drug target of cordycepin in GBC, and the consequences of molecular docking simulation showed that cordycepin could bind TOP2A protein with high affinity. TOP2A was highly expressed in GBC tissues and cells, silence of which could repress the malignant phenotypes and aerobic glycolysis of GBC cells. Besides, TOP2A overexpression reversed the effects induced by cordycepin in GBC cells, which also reversed the suppressed PI3K/AKT pathway. Cordycepin curbs the malignant phenotypes and aerobic glycolysis of GBC via repressing TOP2A-mediated PI3K/AKT pathway.