Ding Ling, Luo Cenxin, Weygant Nathaniel, Chen Wutao, Ru Dan, Lai Yi, Wang You, Li He
Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
Sci Rep. 2025 May 27;15(1):18472. doi: 10.1038/s41598-025-03411-y.
Scutellarin, a natural compound extracted from Scutellaria barbata, has demonstrated antitumor activity in various cancers. However, its role in ovarian cancer has not been fully explored. This study aims to evaluate the therapeutic potential and underlying mechanisms of Scutellarin in ovarian cancer. The effects of Scutellarin on cell proliferation and migration were assessed in ovarian cancer cell lines including SKOV3, A2780, OVCAR3, and OVCAR8. Patient-derived ovarian cancer organoids were used to further validate the in vitro findings. Calcein-AM and PI staining were used to analyze cell viability, and ATP assays were performed to assess organoid activity. Western blot was used to evaluate the regulation of METTL5 protein by Scutellarin. The gene and protein expression levels of METTL5 and their association with ovarian cancer prognosis were assessed using the databases The Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), TNMplot, KM-plotter and The Cancer Genome Atlas (TCGA). The functional role of METTL5 was assessed by transwell migration and colony formation assays, and its involvement in Scutellarin's mechanism of action was confirmed by rescue experiments using wound healing and transwell assays. Scutellarin significantly inhibited the proliferation and migration of ovarian cancer cells. In organoid models, Scutellarin markedly reduced organoid growth, induced cell damage, and decreased ATP levels. Compared to normal ovarian tissue, ovarian cancer tissue exhibited elevated RNA and protein expression levels of METTL5. High METTL5 expression was associated with poorer prognosis in ovarian cancer patients and promoted the migration and clonogenicity of ovarian cancer cells. Scutellarin downregulated METTL5 expression, and rescue experiments demonstrated that Scutellarin inhibited ovarian cancer migration by targeting METTL5. Scutellarin demonstrates potent, broad-spectrum anti-tumor activity in ovarian cancer cell lines, potentially mediated through targeting METTL5. These findings suggest a novel and promising therapeutic strategy for ovarian cancer treatment.
野黄芩苷是从半枝莲中提取的一种天然化合物，已在多种癌症中显示出抗肿瘤活性。然而，其在卵巢癌中的作用尚未得到充分研究。本研究旨在评估野黄芩苷在卵巢癌中的治疗潜力及潜在机制。在包括SKOV3、A2780、OVCAR3和OVCAR8在内的卵巢癌细胞系中评估了野黄芩苷对细胞增殖和迁移的影响。使用患者来源的卵巢癌类器官进一步验证体外研究结果。采用钙黄绿素-AM和PI染色分析细胞活力，并进行ATP检测以评估类器官活性。使用蛋白质免疫印迹法评估野黄芩苷对METTL5蛋白的调控。利用人类蛋白质图谱（HPA）、基因表达谱交互式分析2（GEPIA2）、TNMplot、KM-plotter和癌症基因组图谱（TCGA）数据库评估METTL5的基因和蛋白表达水平及其与卵巢癌预后的关联。通过Transwell迁移和集落形成试验评估METTL5的功能作用，并使用伤口愈合和Transwell试验的挽救实验证实其参与野黄芩苷的作用机制。野黄芩苷显著抑制卵巢癌细胞的增殖和迁移。在类器官模型中，野黄芩苷显著降低类器官生长，诱导细胞损伤并降低ATP水平。与正常卵巢组织相比，卵巢癌组织中METTL5的RNA和蛋白表达水平升高。METTL5高表达与卵巢癌患者较差的预后相关，并促进卵巢癌细胞的迁移和克隆形成能力。野黄芩苷下调METTL5表达，挽救实验表明野黄芩苷通过靶向METTL5抑制卵巢癌迁移。野黄芩苷在卵巢癌细胞系中显示出强大的广谱抗肿瘤活性，可能通过靶向METTL5介导。这些发现为卵巢癌治疗提出了一种新的、有前景的治疗策略。
