Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.
Spine (Phila Pa 1976). 2020 Feb 1;45(3):E126-E139. doi: 10.1097/BRS.0000000000003217.
Xenograft osteosarcoma mouse model.
We determined the effect of lycorine on osteosarcoma.
Osteosarcoma is an aggressive malignant neoplasm, is most prevalent in teenagers and adults and current treatment approaches have reached a survival plateau and attempts to improve osteosarcoma prognosis have proven unsuccessful. Thus there is clear evidence that development of new agents with high efficacy and fewer side effects to provide better prognostic outcome is urgently needed.
The toxicity, function and mechanism of lycorine (LY) on osteosarcoma were accessed in vitro by CCK-8 assay, flow cytometry, and western blotting and in vivo by the xenograft osteosarcoma mouse model.
In this study, we found that LY exhibited dose-dependent and time-dependent cytotoxic effects on human osteosarcoma cell-lines SJSA-1 and U2OS, inducing G1 phase cell cycle arrest and cellular death via apoptosis. Mechanistically, LY treatment elevated ROS generation that activates the p38 mitogen-activated protein kinases (MAPKs) and p53-dependent apoptotic program. Inhibition of ROS generation by NAC or p38 MAPK signaling by SB203580 attenuated the p53-mediated cell cycle arrest and apoptosis induced by LY. In vivo administration of LY markedly reduced tumor growth with little organ-related toxicity in a mouse xenograft model of osteosarcoma.
Collectively, our data suggests that LY exhibit therapeutic potential for the treatment of osteosarcoma.
N/A.
异种移植骨肉瘤小鼠模型。
我们确定石蒜碱对骨肉瘤的影响。
骨肉瘤是一种侵袭性恶性肿瘤,最常见于青少年和成年人,目前的治疗方法已经达到了生存的瓶颈,试图改善骨肉瘤的预后已经证明是不成功的。因此,有明确的证据表明,迫切需要开发具有高效、低副作用的新药物,以提供更好的预后结果。
通过 CCK-8 测定法、流式细胞术和 Western blot 法在体外评估石蒜碱(LY)对骨肉瘤的毒性、功能和机制,并通过异种移植骨肉瘤小鼠模型进行体内评估。
在这项研究中,我们发现 LY 对人骨肉瘤细胞系 SJSA-1 和 U2OS 表现出剂量和时间依赖性的细胞毒性作用,通过细胞凋亡诱导 G1 期细胞周期停滞和细胞死亡。机制上,LY 处理会增加 ROS 的产生,从而激活 p38 丝裂原激活蛋白激酶(MAPKs)和 p53 依赖性凋亡程序。通过 NAC 抑制 ROS 的产生或通过 SB203580 抑制 p38 MAPK 信号转导,可减弱 LY 诱导的 p53 介导的细胞周期停滞和凋亡。LY 在骨肉瘤小鼠异种移植模型中的体内给药可显著抑制肿瘤生长,且对器官相关毒性较小。
总的来说,我们的数据表明 LY 对骨肉瘤的治疗具有潜在的治疗作用。
无。