Ren Lili, Fang Ziru, Xu Jiaojiao, Wu Xiaoxiao, Zhang Yongjun, Cai Hu, Han Zhicun
Department of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Medical Sciences, Hangzhou, Zhejiang 310022, China.
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Balkan Med J. 2025 Jan 2;42(1):54-65. doi: 10.4274/balkanmedj.galenos.2024.2024-8-49.
Breast cancer (BC) is the most prevalent solid cancer affecting women's health globally. Matrine (MAT), a traditional Chinese herb, has exhibited antitumor effects against BC. However, its mechanism of action, particularly whether it involves the control of cell proliferation and epithelial-mesenchymal transition (EMT), remains unknown.
To explore MAT's role in BC and its regulatory mechanisms, as well as to identify targets for the development of novel medicines and improvement of BC treatment modalities.
Experimental study.
The UALCAN and Lnc2Cancer 3.0 databases were used to predict the expression of LINC01116 in BC. The BC cells (MDA-MB-231 and MCF-7) were treated with various concentrations of MAT, and the optimal dose and timing of MAT action were determined using CCK-8 and quantitative real-time polymerase chain reaction assays. Functional assays such as CCK-8, EdU, Transwell, Western blot, and flow cytometry assays were performed on the BC cells, and the impacts of LINC01116, miR-9-5p, and ITGB1 expression levels on MAT's mechanism of action were assessed. The association between LINC01116, miR-9-5p, and ITGB1 was evaluated using dual luciferase and RNA immunoprecipitation assays. Furthermore, the size and weight of the subcutaneous tumors in mice model were assessed. The effect of LINC01116 overexpression on the in vivo action of MAT and histopathological staining (TUNEL immunofluorescence, hematoxylin & eosin staining, immunohistochemistry staining for Ki67 and Bax) were also assessed.
The optimal dose and duration of MAT administration were 8 μm and 24 h, respectively. MAT effectively inhibited BC cell proliferation, EMT progression, and biological functions, while promoting BC cell apoptosis. The animal model experiments also demonstrated that MAT inhibited BC tumor growth in vivo. Furthermore, MAT inhibited LINC01116, which acted as a sponge for miR-9-5p, increasing the ITGB1 level.
MAT suppresses BC cell and EMT proliferation via the LINC01116/miR-9-5p/ITGB1 pathway. Thus, MAT may be a promising target for adjuvant anti-BC therapy.
乳腺癌（BC）是全球影响女性健康的最常见实体癌。苦参碱（MAT）是一种传统中药，已显示出对BC的抗肿瘤作用。然而，其作用机制，特别是是否涉及细胞增殖控制和上皮-间质转化（EMT），仍不清楚。
探讨MAT在BC中的作用及其调控机制，以及确定新药开发和改善BC治疗方式的靶点。
实验研究。
使用UALCAN和Lnc2Cancer 3.0数据库预测LINC0111 在BC中的表达。用不同浓度的MAT处理BC细胞（MDA-MB-231和MCF-7），并使用CCK-8和定量实时聚合酶链反应测定法确定MAT作用的最佳剂量和时间。对BC细胞进行CCK-8、EdU、Transwell、蛋白质免疫印迹和流式细胞术等功能测定，并评估LINC01116、miR-9-5p和ITGB1表达水平对MAT作用机制的影响。使用双荧光素酶和RNA免疫沉淀测定法评估LINC01116、miR-9-5p和ITGB1之间的关联。此外，评估小鼠模型中皮下肿瘤的大小和重量。还评估了LINC01116过表达对MAT体内作用和组织病理学染色（TUNEL免疫荧光、苏木精和伊红染色、Ki67和Bax免疫组织化学染色）的影响。
MAT给药的最佳剂量和持续时间分别为8μm和24小时。MAT有效抑制BC细胞增殖、EMT进程和生物学功能，同时促进BC细胞凋亡。动物模型实验还表明MAT在体内抑制BC肿瘤生长。此外，MAT抑制LINC01116，其作为miR-9-5p的海绵，增加ITGB1水平。
MAT通过LINC01116/miR-9-5p/ITGB1途径抑制BC细胞和EMT增殖。因此MAT可能是辅助抗BC治疗的有希望的靶点。
