尿道膀胱上皮癌(UBUC)占据了约90%的膀胱癌症例数，并且主流治疗方法是经尿道膀胱肿瘤切除术后行膀胱内注射。由于膀胱癌的高死亡率、复发率和进展率，刺激了对替代辅助治疗探索的需求。本研究旨在研究褪黑素在膀胱癌治疗中作为辅助治疗的潜力。细胞活力和克隆能力通过MTT试验和胚胞形成率来评估。细胞周期和凋亡分析是通过流式细胞术和Hoechst 33342染色来完成的，而细胞的转移能力是通过伤口愈合和Transwell试验来测量的。潜在机制是通过肿瘤组学阵列和西方印迹来进行研究的。褪黑素治疗显著降低了T24和UMUC3膀胱癌细胞的增殖和克隆能力。T24和UMUC3细胞中的G1期停滞和亚G1积累导致细胞增殖抑制和细胞死亡，Hoechst 33342染色进一步验证了褪黑素直接诱导细胞凋亡的作用。此外，褪黑素减弱了细胞的运动能力和侵袭性。基于肿瘤组学阵列结果，我们证明褪黑素通过下调HIF-1α和NF-κB通路及下游通路，包括Bcl-2，在UBUC细胞中诱导细胞周期阻滞和凋亡，从而发挥其抗癌作用。总的来说，这些发现支持了褪黑素作为膀胱癌辅助治疗的潜力。

Urinary bladder urothelial carcinoma (UBUC) encompasses about 90% of all bladder cancer cases, and the mainstream treatment is the transurethral resection of the bladder tumor followed by intravesical instillation. High rates of mortality, recurrence, and progression in bladder cancer have stimulated the search for alternative adjuvant therapies. The aim of this study was to investigate the potential of melatonin as adjuvant therapy in bladder cancer. Cell viability and clonogenic ability were assessed by an MTT assay and colony formation. Cell cycle and apoptosis analysis were performed by flow cytometry and Hoechst 33342 staining, while cell metastasis capacity was measured by wound healing and transwell assays. Potential mechanisms were investigated by an oncology array and verified via western blotting. The melatonin treatment significantly reduced T24 and UMUC3 bladder cancer cell proliferation and clonogenic ability. G1 arrest and sub-G1 accumulation in the T24 and UMUC3 cells led to cell proliferation suppression and cell death, and Hoechst 33342 staining further verified the apoptosis induction directly by melatonin. Moreover, melatonin weakened cell motility and invasiveness. Based on the oncology array results, we demonstrated that melatonin exerts its anti-cancer effect by down-regulating the HIF-1α and NF-κB pathways and downstream pathways, including Bcl-2, leading to cell cycle arrest and apoptosis induction in the UBUC cells. Overall, these findings support the potential of melatonin as adjuvant therapy in bladder cancer.