含溴结构域和 WD 重复结构域的蛋白 3 (BRWD3) 在肺腺癌 (LUAD) 组织和细胞中表现出高表达；然而，其在砷引起的毒理学反应中的作用仍不清楚。本研究旨在探讨砷诱导条件下 BRWD3 的表达及其对 BRWD3 敲除后 LUAD 细胞系 SPC-A1 增殖和凋亡的影响。结果显示，用亚砷酸钠 (NaAsO2) 处理的 SPC-A1 细胞中 BRWD3 表达降低，但亚砷酸钠代谢物却没有降低。 BRWD3 敲低抑制 SPC-A1 细胞的细胞增殖并诱导细胞凋亡。 Western blot 分析显示，BRWD3 敲低导致 p53、磷酸化 p53-Ser392 及其下游因子（包括 MDM2、Bak 和 Bax）上调。此外，我们还观察到 p65、磷酸化 p65-Ser276、磷酸化 p65-Ser536 及其下游因子（包括 IκBα、BIRC3、XIAP 和 CIAP1）的下调。此外，聚合酶链反应分析表明，BRWD3敲低还导致增殖相关基因下调和凋亡相关基因上调。总之，BRWD3 通过 p53 和 p65 途径介导砷暴露的增殖和凋亡，这表明砷下调 BRWD3 对 LUAD 治疗具有潜在影响。

Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.