Xu Jingze, Cheng Xinyang, Xu Mengmeng, Zhang Jun, Yang Tianyu, Shuai Lixiong, Deng Lifeng, Zhang Yongsheng
Department of Pathology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu Province, 215004, P. R. China.
Department of Pathology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215123, P. R. China.
BMC Cancer. 2025 Jun 2;25(1):987. doi: 10.1186/s12885-025-13463-y.
Berbamine (BBM) has been reported to play an important role in the anti-inflammatory and anti-neoplastic activities. However, whether BBM mediates the anti-tumor efficacy in renal cell carcinoma (RCC) cells and the potential molecular mechanisms remain unclear.
The effects of BBM on the proliferation, colony formation, cell cycle, cell migration and invasion abilities were performed in RCC cells 786-O and OSRC2, and the effect of BBM on tumor formation was further explored. Furthermore, the effects of BBM on the expression of fat mass and obesity associated gene (FTO) and its target genes were investigated. Finally, the effects of BBM on the proliferation, and invasion of RCC cells after knockdown of FTO were detected.
BBM effectively inhibited the proliferation, migration and invasion of RCC cells in a dose-dependent manner, and BBM also significantly inhibited the growth of tumor in vivo, which has fewer toxic effects on the other organs. Molecular mechanistic studies showed that BBM significantly promoted the expression of FTO mRNA and protein in RCC cells, and knock-down of FTO by siRNA transfection reversed the inhibitory effect of BBM on the growth and invasion of RCC cells.
Collectively, our findings revealed that targeting the tumor suppressive FTO by BBM is a new option to inhibit RCC cells growth and metastasis, providing a good drug candidate potential for development novel therapeutics against metastatic RCC.
已有报道称小檗胺（BBM）在抗炎和抗肿瘤活性中发挥重要作用。然而，BBM是否介导肾细胞癌（RCC）细胞的抗肿瘤疗效及其潜在分子机制仍不清楚。
在RCC细胞786 - O和OSRC2中研究BBM对细胞增殖、集落形成、细胞周期、细胞迁移和侵袭能力的影响，并进一步探讨BBM对肿瘤形成的作用。此外，研究BBM对脂肪量和肥胖相关基因（FTO）及其靶基因表达的影响。最后，检测敲低FTO后BBM对RCC细胞增殖和侵袭的影响。
BBM以剂量依赖性方式有效抑制RCC细胞的增殖、迁移和侵袭，并且BBM在体内也显著抑制肿瘤生长，对其他器官的毒性作用较小。分子机制研究表明，BBM显著促进RCC细胞中FTO mRNA和蛋白的表达，通过siRNA转染敲低FTO可逆转BBM对RCC细胞生长和侵袭的抑制作用。
总体而言，我们的研究结果表明，BBM靶向肿瘤抑制因子FTO是抑制RCC细胞生长和转移的新选择，为开发针对转移性RCC的新型治疗药物提供了良好的候选药物潜力。
