To Explore The Mechanism Of Curcumol On Bladder Cancer Based On Network Pharmacology Analysis And Experimental Study

Objective : Bladder cancer is one of the ten most common malignant tumors in the world,which is characterized by a high incidence,high recurrence rate and high mortality rate.According to the depth of tumor invasion,bladder cancer can be divided into non-muscle-invasive bladder cancer(NMIBC)and muscle-invasive bladder cancer(MIBC).Although radical cystectomy,systemic chemotherapy,targeted therapy,and immunotherapy have significantly improved treatment outcomes of bladder cancer.The overall survival rate is still unsatisfactory due to the high recurrence and metastasis rates.Therefore,it is urgent to explore and develop adjuvant drug for the treatment of bladder cancer.Evidence shows the potential of natural compounds in the treatment of bladder cancer.Curcumol(Cur)is one of the main bioactive components of traditional Chinese medicinal plant Rhizoma Curcumae.It has various pharmacological properties such as antitumor,anti-proliferation,anti‐inflammatory,antioxidant,and antimicrobial activities with low toxicity.However,the application of Cur in the treatment of bladder cancer and its underlying molecular mechanisms require further research.Hence,we analyze the molecular mechanism and key targets of Cur by network-pharmacology and molecular docking verified in vitro cells experiments.Method:1.The potential targets of Cur were screened through the Swiss Target Prediction and Pharm Mapper databanks.At the same time,BLCA-related genes were retrieved from 5 databases including Gene Cards,OMIM,Mala Cards,Dis Gent,KEGG.Then,the drug targets of Cur were intersected with BLCA-related genes to obtain the intersecting genes,and a Protein-Protein interaction(PPI)Network and BLCA-Cur Network was constructed to further screen out the hub genes.The GO biological process and KEGG signaling pathway enrichment analysis were performed.Finally,Molecular docking simulations of Cur to hub genes protein structure(Cyclin D1,MDM2)was performed using Auto Dock Vina software.2.Human bladder tumor cell lines(T24 and 5637)were used to explore the effect and underlying mechanism of Cur on bladder cancer.Cell Counting Kit-8(CCK8)experiment and cloning experiment were used to measure cell proliferation.Scratch assay were used to detect cell migration ability.Western blotting was used to detect the expression of MDM2 and PI3K/AKT/Cyclin D1 pathway related proteins.Conclusion:Curcumol exerts an antitumor effect on bladder cancer cells through the regulation of MDM2,E2F1 and PI3K/Akt/Cyclin D1 signaling pathway,curcumol have the potential to be the therapy of bladder cancer.