Wei Zhun, Zheng Di, Pi Wenfeng, Qiu Yonglong, Xia Kezhou, Guo Weichun
Department of Orthopaedics, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China.
Department of Orthopaedics, Chinese Traditional Medicine of Daye Hospital, Hubei Province, Daye 435100, China.
J Bone Oncol. 2023 Jan 3;38:100468. doi: 10.1016/j.jbo.2023.100468. eCollection 2023 Feb.
Currently, chemotherapeutic drugs are widely used for the treatment of osteosarcoma. However, many of these drugs exhibit shortcomings such as poor efficacy, high toxicity, and tolerance. Isoquercitrin (ISO) is a traditional Chinese medicine that has been proved to exert good therapeutic effects on various tumors; however, its role in osteosarcoma has not been reported. Here, we observed that ISO exerted a marked inhibitory effect on the occurrence and development of osteosarcoma in a time- and dose-dependent manner. First, we determined that ISO significantly inhibited proliferation, induced EMT-related migration and invasion and induced apoptosis of osteosarcoma cells . Concurrently, we also observed that both β-catenin and its downstream genes (c-Myc, CyclinD1, and Survivin) were significantly down-regulated. To verify if the anti-tumor effect of ISO was related to the Wnt/β-catenin signaling pathway, we altered the protein expression level of β-catenin using recombinant lentivirus, then we observed that the effects of ISO on the proliferation, metastasis, and apoptosis of osteosarcoma cells were significantly reversed. Additionally, we used a nude mouse xenograft model and observed that ISO significantly inhibited the growth of osteosarcoma and improved the survival rate of the animal models. In conclusion, this study demonstrates that ISO can exert anti-tumor effects in part by inhibiting the Wnt/β-catenin signaling pathway, thus providing a new potential therapeutic strategy for the treatment of osteosarcoma.
目前，化疗药物被广泛用于骨肉瘤的治疗。然而，这些药物中的许多都存在疗效不佳、毒性高和耐受性等缺点。异槲皮苷（ISO）是一种传统中药，已被证明对各种肿瘤具有良好的治疗效果；然而，其在骨肉瘤中的作用尚未见报道。在此，我们观察到ISO对骨肉瘤的发生和发展具有明显的抑制作用，且呈时间和剂量依赖性。首先，我们确定ISO显著抑制骨肉瘤细胞的增殖，诱导与上皮-间质转化（EMT）相关的迁移和侵袭，并诱导其凋亡。同时，我们还观察到β-连环蛋白及其下游基因（c-Myc、细胞周期蛋白D1和生存素）均显著下调。为了验证ISO的抗肿瘤作用是否与Wnt/β-连环蛋白信号通路有关，我们使用重组慢病毒改变β-连环蛋白的蛋白表达水平，然后观察到ISO对骨肉瘤细胞增殖、转移和凋亡的影响均被显著逆转。此外，我们使用裸鼠异种移植模型，观察到ISO显著抑制骨肉瘤的生长并提高动物模型的存活率。总之，本研究表明ISO可部分通过抑制Wnt/β-连环蛋白信号通路发挥抗肿瘤作用，从而为骨肉瘤的治疗提供一种新的潜在治疗策略。
