Xie Tianyu, Liang Jiming, Lin Chengsen, Feng Wenyu, Yang Mingxiu, Li Shanhang, Xiong Liang, Luo Kai, Li Feicui, Tang Shengping, Liu Shangyu, Huang Qian, Liao Shijie, Liu Jianhong, Cai Yangjie, Tang Fuxing, Tang Haijun, Wei Qingjun, Lin Yunhua, Liu Yun
Department of Traumatic Orthopaedic, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China.
Department of Spine and Orthopedic Surgery, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China.
APL Bioeng. 2025 Aug 8;9(3):036110. doi: 10.1063/5.0266780. eCollection 2025 Sep.
As the most common primary malignant bone tumor, osteosarcoma (OS) is characterized by drug resistance and poor prognosis, highlighting the urgent need for promising therapeutic agents. Formononetin (FMN), a natural product derived from , has been reported to possess anti-tumor properties. However, its role in OS has not yet been elucidated. In the present study, we established an OS patient-derived xenograft model to investigate the effects of FMN and the underlying mechanisms of its effects on OS. When FMN treatment was completed, bulk transcriptome sequencing was conducted, and the analyses were combined with OS single-cell RNA sequencing (scRNA-seq) data. Results indicated that GTSF1 was up-regulated in OS but down-regulated after FMN intervention, which may regulate the apoptosis of OS cells. Furthermore, the qRT-PCR and IHC results demonstrated that GTSF1 expression was significantly up-regulated in OS cells, whereas FMN expression was down-regulated both and . Moreover, experiments revealed that FMN effectively promoted apoptosis and suppressed the proliferation, migration, and invasion of OS cells. Therefore, this study demonstrated that FMN exerts anti-OS effects by down-regulating GTSF1 expression, thus effectively promoting the apoptosis and inhibiting the proliferation of OS cells, making FMN a promising anti-OS drug.
作为最常见的原发性恶性骨肿瘤，骨肉瘤（OS）具有耐药性且预后较差，这凸显了对有前景的治疗药物的迫切需求。芒柄花黄素（FMN）是一种从[来源未提及]中提取的天然产物，据报道具有抗肿瘤特性。然而，其在骨肉瘤中的作用尚未阐明。在本研究中，我们建立了一个源自骨肉瘤患者的异种移植模型，以研究芒柄花黄素的作用及其对骨肉瘤作用的潜在机制。当芒柄花黄素治疗完成后，进行了整体转录组测序，并将分析结果与骨肉瘤单细胞RNA测序（scRNA-seq）数据相结合。结果表明，GTSF1在骨肉瘤中上调，但在芒柄花黄素干预后下调，这可能调节骨肉瘤细胞的凋亡。此外，qRT-PCR和免疫组化结果表明，GTSF1在骨肉瘤细胞中表达显著上调，而芒柄花黄素在[具体情况未明确]中均下调。而且[此处原文表述不完整]实验表明，芒柄花黄素有效促进凋亡并抑制骨肉瘤细胞的增殖、迁移和侵袭。因此，本研究表明芒柄花黄素通过下调GTSF1表达发挥抗骨肉瘤作用，从而有效促进骨肉瘤细胞凋亡并抑制其增殖，使芒柄花黄素成为一种有前景的抗骨肉瘤药物。
