Ganesan Kumar, Xu Cong, Wu Song, Sui Yue, Du Bing, Zhang Jinhui, Gao Fei, Chen Jianping, Tang Hailin
School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Research (Wash D C). 2024 Dec 16;7:0553. doi: 10.34133/research.0553. eCollection 2024.
Breast cancer (BC) often spreads to bones, leading to bone metastasis (BM). Current targeted therapies have limited effectiveness in the treatment of this condition. Osteoclasts, which contribute to bone destruction, are crucial in supporting tumor cell growth in the bones. Breast cancer bone metastasis (BCBM) treatments have limited efficacy and can cause adverse effects. Ononin exhibits anticancer properties against various cancers. The study examined the impact of ononin on the BCBM and the signaling pathways involved. Our study utilized a variety of experimental techniques, including cell viability assays, colony formation assays, wound-healing assays, Transwell migration assays, Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) staining. We examined the effects of ononin on osteoclastogenesis induced in MDA-MB-231 conditioned medium- and RANKL-treated RAW 264.7 cells. In a mouse model of BCBM, ononin reduced tumor-induced bone destruction. Ononin treatment effectively inhibited proliferation and colony formation and reduced the metastatic capabilities of MDA-MB-231 cells by suppressing cell adhesion, invasiveness, and motility and reversing epithelial-mesenchymal transition (EMT) markers. Ononin markedly suppressed osteoclast formation and osteolysis-associated factors in MDA-MB-231 cells, as well as blocked the activation of the mitogen-activated protein kinase (MAPK) pathway in RAW 264.7 cells. Ononin treatment down-regulated the phosphorylation of MAPK signaling pathways, as confirmed using MAPK agonists or inhibitors. Ononin treatment had no adverse effects on the organ function. Our findings suggest that ononin has therapeutic potential as a BCBM treatment by targeting the MAPK pathway.
乳腺癌（BC）常转移至骨骼，导致骨转移（BM）。目前的靶向治疗在这种疾病的治疗中效果有限。破骨细胞参与骨质破坏，在支持肿瘤细胞在骨骼中生长方面至关重要。乳腺癌骨转移（BCBM）治疗疗效有限且会引起不良反应。鹰嘴豆芽素A对多种癌症具有抗癌特性。该研究考察了鹰嘴豆芽素A对BCBM及相关信号通路的影响。我们的研究采用了多种实验技术，包括细胞活力测定、集落形成测定、伤口愈合测定、Transwell迁移测定、蛋白质印迹分析以及抗酒石酸酸性磷酸酶（TRAP）染色。我们研究了鹰嘴豆芽素A对在MDA - MB - 231条件培养基和RANKL处理的RAW 264.7细胞中诱导的破骨细胞生成的影响。在BCBM小鼠模型中，鹰嘴豆芽素A减少了肿瘤诱导的骨质破坏。鹰嘴豆芽素A治疗通过抑制细胞粘附、侵袭和运动能力以及逆转上皮 - 间质转化（EMT）标志物，有效抑制了MDA - MB - 231细胞的增殖和集落形成，并降低了其转移能力。鹰嘴豆芽素A显著抑制MDA - MB - 231细胞中的破骨细胞形成和骨溶解相关因子，同时阻断RAW 264.7细胞中丝裂原活化蛋白激酶（MAPK）途径的激活。使用MAPK激动剂或抑制剂证实，鹰嘴豆芽素A治疗下调了MAPK信号通路的磷酸化。鹰嘴豆芽素A治疗对器官功能没有不良影响。我们的研究结果表明，鹰嘴豆芽素A通过靶向MAPK途径具有作为BCBM治疗方法的治疗潜力。
