The Therapeutic Effect Of Cuprous Oxide Nanoparticles In Bladder Cancer

【Background】Bladder cancer is one of the most common malignant tumor in the urological system in the world.The incidence rate is the sixth in male malignant tumors,and the first among all the malignant tumors in the urological system in China.Bladder cancer is categorized into non-muscle-invasive bladder cancer(NMIBC)or muscle-invasive bladder cancer(MIBC)according to pathological stage.More than 75% patients were diagnosed as NMIBC,they are usually treated by transurethral resection of bladder tumor(TURBT)and bladder intravesical instillation.While a large number of clinical evidence suggests that,currently,intravesical drugs are still with significant drug side effects,and poor treatment effect and other issues,which starves for researching and developing new infusion drugs.Inorganic nano drugs can be effective candidate exhibit many unique advantages as new anti-tumor choice.Cuprous oxide nanoparticles(CONPs)is a copper-bearing inorganic nano-materials are with various important characteristics of nano-materials.CONPs have potential for clinical application for BCa therapy.【Objective】This research mainly discuss the anti-tumor effect of CONPs for bladder urothelial carcinoma and explore the mechanism of it.【Methods】In vitro treatment,bladder cancer cells were treated with CONPs.CCK8-kit was applied to test the inhibition efficiency of CONPs for various bladder urothelial carcinoma cell line and human normal urothelial cell and human fibroblast cell.Flow Cytometry analysis was performed to investigate the impact of CONPs on bladder cancer cell cycle.Annexin V-FITC/PI apoptosis detection was performed to evaluate the influence of CONPs on bladder cancer cell apoptosis.Transwell invasion was performed to evaluate the influence of CONPs on migration and invasion ability of bladder cancer cells.bladder cancer cells.A T24-implanted nude mice model was used to study the effect of CONPs in vivo.Related proteins markers of autophagy and apoptosis were detected by Western blot.【Results】In vitro,CONPs can effectively kill various bladder urothelial carcinoma cell lines and had less cytotoxic effect on human urinary epithelial cell lines and fibroblast cell lines than tumor cell lines.Through the Flow Cytometry detection,CONPs were found to induce apoptosis,and lead to cell cycle arrest at G2/M phase in T24 and 5637 cells.Transwell assay suggests that migration and invasion ability of bladder cancer cells was significantly inhibited by CONPs.Experiments in vitro showed that,compared with the control group,CONPs treatment group significantly reduced the volume of subcutaneous tumors and inhibited tumor growth significantly.At the same time,there was no significant difference between the two groups in body weight change among CONPs treatment group and control group.Liver,kidney,lung,spleen and heart showed no significant change after treatment,demonstrate that CONPs effectively inhibit the tumor at the same time,with high security.Western blot analysis showed that low doses of CONPs for bladder cancer cells may up-regulate ATG5,ATG7 and LC3 B protein expression by,suggests that CONPs are closely related to the occurrence of autophagy in bladder cancer cells.In conclusion.【Conclusion】This study showed that low CONPs can induce both apoptosis and autophagy of bladder cancer.Performed certificated anti-tumor effect both in vitro and vivo and could be used as a novel inorganic nano-drug for bladder cancer.