Hüseyin BAL, Bensu KOZAN, Özge ÇEVİK
Meandros Medical and Dental Journal - 2026;27(3):473-480
Objective: Combination therapies have emerged as promising strategies in cancer treatment; therefore, this study aimed to investigate the therapeutic efficacy and underlying molecular mechanisms of pemetrexed and mitomycin -C combination therapy in bladder cancer cell s. Pemetrexed reduces cancer cell proliferation by impairing DNA and RNA biosynthesis, whereas mitomycin -C induces cytotoxicity through disruption of DNA. Materials and Methods: The cytotoxic effects of the pemetrexed -mitomycin -C combination was evaluated in human bladder cancer cells (UM -UC-3) via Annexin V/PI -based flow cytometric analysis, followed by evaluation of DNMT1 mRNA and protein levels. Statistical analyses were performed using indepen dent t- tests. Results: The combined treatment significantly induced apoptosis in bladder cancer cells at low concentrations, demonstrating a markedly synergistic effect. Moreover, the combination markedly suppressed DNMT1 mRNA expression and protein levels, indicating inhibition of aberrant DNA methylation mechanisms associated with cancer progression. Conclusion: These results indicate that co -treatment with pemetrexed and mitomycin -C holds therapeutic potential in metastatic bladder cancer and may inform future efforts to design DNMT1 -targeted inhibitory strategies .
