Tan Qiang, Liu Hongzhan, Shi Qiaojing
Department of Oncology, Affiliated Hospital of Xiangnan University, Chenzhou City, Hunan, China.
Department of Orthopedics, Affiliated Hospital of Xiangnan University, Chenzhou City, Hunan, China.
Chem Biol Drug Des. 2025 Mar;105(3):e70075. doi: 10.1111/cbdd.70075.
Traditional Chinese medicine Ailanthone (AIL) has been confirmed to possess antimalarial, anti-inflammatory, and anticancer effects. Here, this study aimed to excavate the biological role and mechanism of AIL on osteosarcoma (OS) progression. Levels of Regulator of G protein signaling 4 (RGS4) and Twist Family BHLH Transcription Factor 1 (TWIST1) were detected by qRT-PCR and western blotting. In vitro and tumor formation experiments were conducted for functional analysis. The protein interaction between RGS4 and TWIST1 was verified by using a Co-immunoprecipitation assay. AIL impeded the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression, but induced apoptosis in OS cells. RGS4 was highly expressed in OS tissues and cells and was decreased by AIL in cells. RGS4 silencing suppressed the growth and metastasis of OS cells, and RGS4 overexpression reversed the anticancer action of AIL in OS cells. Mechanistically, RGS4 interacted with TWIST1 and positively regulated its expression. TWIST1 was highly expressed in OS tissues and cells and could be reduced by AIL in cells. Moreover, TWIST1 overexpression abolished RGS4 silencing-triggered growth and metastasis inhibition in OS cells. Importantly, AIL impeded OS growth and metastasis in vivo by regulating RGS4 and TWIST1. Ailanthone restrained OS growth and metastasis by decreasing RGS4 and TWIST1 expression.
传统中药臭椿酮（AIL）已被证实具有抗疟疾、抗炎和抗癌作用。在此，本研究旨在挖掘AIL对骨肉瘤（OS）进展的生物学作用及机制。通过qRT-PCR和蛋白质免疫印迹法检测G蛋白信号调节因子4（RGS4）和 Twist 家族 BHLH 转录因子1（TWIST1）的水平。进行体外和肿瘤形成实验以进行功能分析。使用免疫共沉淀试验验证RGS4和TWIST1之间的蛋白质相互作用。AIL可抑制OS细胞的增殖、侵袭、迁移和上皮-间质转化（EMT）进程，但可诱导OS细胞凋亡。RGS4在OS组织和细胞中高表达，在细胞中可被AIL降低。RGS4沉默可抑制OS细胞的生长和转移，RGS4过表达可逆转AIL对OS细胞的抗癌作用。机制上，RGS4与TWIST1相互作用并正向调节其表达。TWIST1在OS组织和细胞中高表达，在细胞中可被AIL降低。此外，TWIST1过表达消除了RGS4沉默触发的OS细胞生长和转移抑制。重要的是，AIL通过调节RGS4和TWIST1在体内抑制OS的生长和转移。臭椿酮通过降低RGS4和TWIST1的表达来抑制OS的生长和转移。
