这项研究旨在探究恩扎鲁胺（ENZ）和三氧化二砷（ATO）联合治疗去势抵抗性前列腺癌（CRPC）的抗肿瘤效应及其机制。首先，利用集落形成实验、FACS分析和DNA断裂检测评估它们对C4-2B细胞的影响。采用 mRNA测序和基因富集分析等生物信息学方法筛选相关靶基因和途径。使用Western blot评估蛋白相关的血管生成、凋亡、DNA修复和筛选的基因的表达水平。最后，在皮下肿瘤模型和异种移植物组织切片中进一步验证了效应。发现ENZ联合ATO不仅可以显著抑制C4-2B细胞增殖和血管生成，还可以诱导细胞停滞和凋亡。此外，它们的联合作用也导致了DNA损伤修复相关途径的中断。Western blot分析进一步表明，这些途径中的蛋白质，特别是P-ATR和P-CHEK1，显著降低。此外，它们的联合作用还抑制了移植物的肿瘤生长。总的来说，ENZ联合ATO通过调节ATR-CHEK1-CDC25C途径，协同提高了治疗效果并抑制了CRPC的进展。

The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.