Chitooligosaccharides inhibit tumor progression and induce autophagy through the activation of the p53/mTOR pathway in osteosarcoma
Chitooligosaccharides inhibit tumor progression and induce autophagy through the activation of the p53/mTOR pathway in osteosarcoma
复制标题
壳寡糖通过激活骨肉瘤中的 p53/mTOR 通路抑制肿瘤进展并诱导自噬
DOI：
10.1016/j.carbpol.2020.117596
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发表时间：
2021-01-31
影响因子：
11.2
通讯作者：
Yang, Qing-cheng
中科院分区：
文献类型：
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作者：
Pan, Zhen;Cheng, Dong-dong;Yang, Qing-cheng
骨肉瘤是最常见的骨原发肉瘤。利用壳寡糖作为药物载体是一种新兴的肿瘤治疗新策略。然而，COS在骨肉瘤中的应用尚未见报道。在此，我们研究了COS对骨肉瘤的影响，并提出了可能的机制。最初，我们通过酶水解获得了低聚合度（DP = 2-6）的COS。体外实验表明，这些COS材料对骨肉瘤细胞具有抗肿瘤活性。我们发现COS对骨肉瘤细胞生长、抑制转移、诱导细胞凋亡和自噬有显著影响，并通过p53/mTOR信号通路触发骨肉瘤细胞凋亡自噬。此外，COS还能抑制异种骨肉瘤模型体内肿瘤的生长和转移。最后，我们发现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可能是治疗骨肉瘤的新的潜在候选药物。
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.