Pan Haitao, Li Congshu, Wang Mengyao, Ye Kang, Fan Xiaohui, Fu Yongping, Yang Jihong, Li Zhenhao
BoYu Intelligent Health Innovation Laboratory, Hangzhou, 311121, Zhejiang, China.
Zhejiang Research Institute of Traditional Chinese Medicine, Hangzhou, 310012, Zhejiang, China.
Sci Rep. 2025 Jul 1;15(1):22111. doi: 10.1038/s41598-025-05890-5.
Osteosarcoma (OS) is a severe malignancy affecting children and adolescents, with limited effective treatments leading to poor outcomes. This study explored the potential of sporoderm-removed Ganoderma lucidum spores (RGLS) as a novel therapeutic agent against OS and elucidated its mechanism of action. Our in vivo and in vitro experiments showed that RGLS significantly inhibited S-180 OS cell proliferation, while simultaneously inducing apoptosis. Multi-omics analysis revealed that RGLS disrupted glycerophospholipid metabolism by upregulating lysophosphatidylcholine (LysoPC) levels through phospholipase A2 (PLA2)-mediated pathways. Co-culture assays further demonstrated that RGLS promoted the endocytosis of macrophage-derived Pla2g7 protein into S-180 cells, enhancing its anti-cancer effects. Additionally, RGLS modulated the cellular fatty acid profile and suppressed the β-oxidation of long-chain fatty acids, leading to energy depletion in OS cells. These findings provide a novel view of the multi-targeted mechanisms of RGLS, positioning it as a promising candidate for OS therapy.
骨肉瘤（OS）是一种影响儿童和青少年的严重恶性肿瘤，有效治疗方法有限，导致预后不良。本研究探讨了去壁灵芝孢子（RGLS）作为一种新型抗骨肉瘤治疗药物的潜力，并阐明了其作用机制。我们的体内和体外实验表明，RGLS显著抑制S-180骨肉瘤细胞增殖，同时诱导细胞凋亡。多组学分析显示，RGLS通过磷脂酶A2（PLA2）介导的途径上调溶血磷脂酰胆碱（LysoPC）水平，从而破坏甘油磷脂代谢。共培养实验进一步证明，RGLS促进巨噬细胞来源的Pla2g7蛋白内吞进入S-180细胞，增强其抗癌作用。此外，RGLS调节细胞脂肪酸谱，抑制长链脂肪酸的β-氧化，导致骨肉瘤细胞能量耗竭。这些发现为RGLS的多靶点作用机制提供了新的视角，使其成为骨肉瘤治疗的一个有前景的候选药物。
