Objective: Limited research has been conducted on the impact of semaglutide on bladder cancer in individuals with obesity. Hence, this study employed proteomics in conjunction with bioinformatics technology to demonstrate that semaglutide potentially operates through a mechanism that reduces the likelihood of bladder cancer among obese patients.
Methods: Thirty-six healthy male C57BL/6J mice were randomly divided into normal diet group (NCD group), high fat diet group (HFD group) and high fat diet group (Sema group). Serum indexes and SOD levels were measured, and tandem mass spectrometry combined with liquid chromatography-tandem mass spectrometry analysis was used to identify differentially expressed proteins. Bioinformatics technology was used to further analyze differentially expressed proteins, so as to explore the potential mechanism of semaglutide in reducing bladder cancer risk.
Result: In the obesity model induced by a high-fat diet, semaglutide administration resulted in decreased body weight, improved lipid profile, blood glucose levels, and enhanced antioxidant stress capacity in mice. Differential expression proteins (DEPs) were found in various cellular components such as cytoplasm, cell membrane, and nucleus. Biological processes (BPs) were enriched in fatty acid metabolism and regulation of response to external stimuli. Comparative analysis of gene expression revealed that Lama2, Lama4, Lamc1, and Thbs2 primarily participated in the extracellular matrix (ECM) pathway. Their expression was up-regulated in the high-fat group but down-regulated after treatment with semaglutide.
Conclusion: Semaglutide exhibits potential in ameliorating high-fat diet-induced obesity and delaying the onset and progression of bladder cancer. The involvement of Lama2, Lama4, Lamc1, Thbs2 in the extracellular matrix pathway may underlie semaglutide's mechanism of action against bladder cancer.
Y. Liu: None. S. Chen: None. J. Ban: None. Z. Li: None.
