فهرست نشریات علمی دسترسی آزاد ایران

Background and Objectives: Hypertension and bladder cancer are frequently co-diagnosed in individuals who require blood pressure management and anti-cancer therapies. Immunotherapy has revolutionized cancer treatment. However, the role and clinical significance of the first-line anti-hypertensive drug amlodipine in immunotherapy outcomes remains largely elusive. To evaluate the role of amlodipine in enhancing the efficacy of anti-PD1 immunotherapy and its underlying mechanisms in bladder cancer.    Methods: Basic research methods were used in the present work. A murine syngeneic bladder cancer and melanoma model was employed to evaluate the therapeutic effect of the combination of amlodipine with anti-PD1. Additionally, immunohistochemistry was utilized to quantify CD8+ T cells and Ki67+ cells. Finally, several in-vitro and in-vivo assays were performed to explore the effects of amlodipine on human bladder cancer cells, and bioinformatics analysis and qPCR were conducted to explore the underlying mechanism.   Results: Amlodipine enhanced the tumor-inhibitory effects of anti-PD1 therapy, in line with the results in the melanoma model. Furthermore, the results of in-vitro and in-vivo experiments utilizing UMUC3 human bladder cancer cells revealed that amlodipine significantly suppressed tumor progression. Meanwhile, the results of in-vitro and in-vivo experiments demonstrated that amlodipine regulated NFAT2 expression, with the loss of inhibition following NFAT2 knockdown.    Conclusion: These results indicated that amlodipine suppresses tumor growth by regulating NFAT2 expression and enhancing anti-PD1 therapy effects. Indeed, these findings position amlodipine as an effective adjunctive therapy in bladder cancer treatment. Nevertheless, further mechanistic studies and clinical trials are warranted.