Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Carbohydr Polym. 2021 Apr 15;258:117596. doi: 10.1016/j.carbpol.2020.117596. Epub 2021 Jan 21.
Osteosarcoma is the most common primary sarcoma of bone. The use of Chitooligosaccharide (COS) as a drug carrier is an emerging new strategy for cancer therapy. However, the application of COS in osteosarcoma has not been reported. Here, we investigated the influence of COS on osteosarcoma, and suggested the underlying mechanism. Initially, we obtained COS with a low-degree-polymerized (DP = 2-6) by enzymatic hydrolysis. Using these COS materials, in vitro assays showed that COS elicited the anti-tumor activity against osteosarcoma cells. We found that COS had significant effects on cell growth, metastasis inhibition, apoptosis and autophagy induction, and triggered pro-apoptosis autophagy through p53/mTOR signaling pathway in osteosarcoma cells. In addition, the COS also inhibited tumor growth and metastasis in an osteosarcoma xenograft model in vivo. Finally, we showed that COS could increase sensitivity to chemotherapy of cisplatin in vitro. Thus, we provide experimental evidence to demonstrate that COS has anti-tumor effect on osteosarcoma, and COS can be a new potential therapeutic candidate for the treatment of osteosarcoma.
骨肉瘤是最常见的原发性骨肉瘤。壳寡糖（COS）作为药物载体的应用是癌症治疗的一种新兴策略。然而，COS 在骨肉瘤中的应用尚未见报道。在这里，我们研究了 COS 对骨肉瘤的影响，并提出了其潜在的机制。首先，我们通过酶解获得了低聚合度（DP=2-6）的 COS。使用这些 COS 材料，体外实验表明，COS 对骨肉瘤细胞具有抗肿瘤活性。我们发现 COS 对细胞生长、转移抑制、凋亡和自噬诱导有显著作用，并通过 p53/mTOR 信号通路诱导促凋亡自噬。此外，COS 还能抑制体内骨肉瘤异种移植模型中的肿瘤生长和转移。最后，我们表明 COS 可以增加体外顺铂化疗的敏感性。因此，我们提供了实验证据，证明 COS 对骨肉瘤具有抗肿瘤作用，COS 可能成为治疗骨肉瘤的一种新的潜在治疗候选物。
