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揭示GSK126对骨肉瘤细胞的影响:对细胞凋亡、自噬和细胞迁移的意义

Unveiling the effects of GSK126 on osteosarcoma cells implications for apoptosis, autophagy, and cellular migration.

作者信息

Xiong Xifeng, Liu Yulin, Du Yanli, Lai Xudong, Si Chunming, Miao Haixiong

机构信息

Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China.

Guangdong Medical University, Zhanjiang, Guangdong, China.

出版信息

Discov Oncol. 2025 Feb 27;16(1):245. doi: 10.1007/s12672-025-02010-7.

Abstract

Osteosarcoma, a malignant bone tumor, faces significant treatment challenges. Enhancer of zeste homolog 2 (EZH2) shows aberrant expression in various tumors including osteosarcoma, which is identified as a potential therapeutic target. The anti-cancer efficacy of EZH2 inhibitor GSK126 has attracted attention, yet its impact on osteosarcoma cells was not fully understood. The study investigated the effects of GSK126 on osteosarcoma cells, particularly in apoptosis, autophagy, and cell motility. Our findings revealed that GSK126 induced apoptosis and autophagy, evidenced by increased markers like cleaved caspase-3 and LC3-II, and decreased cellular migration, through downregulation of the Fuse Binding Protein 1 (FBP1)/C-Myc axis. These findings suggest GSK126 as a promising therapeutic against osteosarcoma, offering a dual action of promoting cell death and hindering migration.

摘要

骨肉瘤是一种恶性骨肿瘤,面临着重大的治疗挑战。zeste同源物2增强子(EZH2)在包括骨肉瘤在内的各种肿瘤中表现出异常表达,被确定为一个潜在的治疗靶点。EZH2抑制剂GSK126的抗癌疗效已引起关注,但其对骨肉瘤细胞的影响尚未完全明确。该研究调查了GSK126对骨肉瘤细胞的影响,特别是在细胞凋亡、自噬和细胞运动方面。我们的研究结果显示,GSK126通过下调融合结合蛋白1(FBP1)/C-Myc轴诱导细胞凋亡和自噬,这表现为裂解的半胱天冬酶-3和LC3-II等标志物增加,以及细胞迁移减少。这些研究结果表明,GSK126有望成为治疗骨肉瘤的药物,具有促进细胞死亡和阻碍迁移的双重作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1c7/11868014/1bae4d57119d/12672_2025_2010_Fig1_HTML.jpg

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