Sun Yuxin, Li Cong, Yin Hang, Li Kunyan, Wang Ying, Zhang Shuailong, Zhao Yi, Wang Jing, Mao Weifeng
College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
J Cell Mol Med. 2025 Sep;29(17):e70836. doi: 10.1111/jcmm.70836.
Berberine (BBR) is an isoquinoline alkaloid with a variety of biological activities, including anti-microbial and anti-tumoral activities. However, the cellular targets of BBR and the roles of BBR in the radiosensitivity of breast cancer cells are not well defined. In this study, we investigated the effects of BBR on the radiosensitivity of BT549 triple-negative breast cancer cells. Through RNA-seq results, we found that BBR significantly down-regulated the expression of DNA ligases. The results of western blot and comet assay confirmed that BBR attenuated DNA ligase III (LIGIII) expression and caused DNA damage in a dose-dependent manner. The results of electron microscopy showed that BBR decreased mitochondrial copies and induced mitochondrial autophagy. Clonal formation analysis showed that BBR sensitised breast cancer cells to irradiation. The genetic complementation and interference assays showed that the effect of BBR on the radiosensitivity of BT549 breast cancer cells is dependent on the expression of LIGIII. These results contribute to the understanding of the effects of BBR on cellular DNA repair and the clinical application of BBR in breast cancer therapy.
黄连素（BBR）是一种具有多种生物活性的异喹啉生物碱，包括抗菌和抗肿瘤活性。然而，BBR的细胞靶点以及BBR在乳腺癌细胞放射敏感性中的作用尚不清楚。在本研究中，我们研究了BBR对BT549三阴性乳腺癌细胞放射敏感性的影响。通过RNA测序结果，我们发现BBR显著下调了DNA连接酶的表达。蛋白质印迹和彗星试验结果证实，BBR以剂量依赖性方式减弱DNA连接酶III（LIGIII）的表达并导致DNA损伤。电子显微镜结果显示，BBR减少了线粒体拷贝数并诱导了线粒体自噬。克隆形成分析表明，BBR使乳腺癌细胞对辐射敏感。基因互补和干扰试验表明，BBR对BT549乳腺癌细胞放射敏感性的影响取决于LIGIII的表达。这些结果有助于理解BBR对细胞DNA修复的影响以及BBR在乳腺癌治疗中的临床应用。
