Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemical Carcinogen-induced Bladder Cancer

<h3>Background/Aim:</h3> The bladder is highly susceptible to chemical carcinogens rendering bladder cancer one of the most prevalent cancers globally. While microsomal prostaglandin E synthase-1 (mPGES-1) is known to promote carcinogenesis in several tissues such as the colon and skin, its involvement in bladder cancer has not been fully investigated. This study aimed to clarify whether mPGES-1 promotes chemically-induced bladder carcinogenesis using a gene-deficient mouse model and evaluate its potential as a novel therapeutic target. <h3>Materials and Methods:</h3> Bladder carcinogenesis was induced using <i>N</i>-butyl-<i>N</i>-(4-hydroxybutyl) nitrosamine (BBN) in mPGES-1 knockout (KO) and littermate wild-type (WT) mice. The incidence and progression of bladder tumors were compared between the two groups through histological analysis. Additionally, biochemical assays were performed, including the measurement of prostanoid levels by liquid chromatography-mass spectrometry (LC/MS/MS) and the analysis of gene expression levels <i>via</i> real-time PCR. <h3>Results:</h3> Incidence of bladder cancer was suppressed in mPGES-1 KO mice compared to WT mice. Histopathological examination revealed less frequent invasion of the muscular layer by tumor cells (muscularis propria) in mPGES-1 KO mice than in WT mice. Cyclooxygenase-2 expression and PGE₂ production were upregulated in bladder tissues following BBN treatment, and PGE₂ production was markedly reduced in bladders of mPGES-1 KO mice. The expression of biomarker genes in macrophages and other inflammatory cells was significantly attenuated by mPGES-1 deficiency. <h3>Conclusion:</h3> mPGES-1 plays an important role in promoting bladder carcinogenesis and cancer progression, including muscle invasion, by upregulating PGE₂ production in the inflammatory microenvironment. Thus, mPGES-1 is a key driver of bladder cancer development and may be a safe therapeutic target for the prevention and treatment of bladder cancer.