He Bin, Zhang Wenkan, He Jiaming
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The Second Affiliated Hospital, Zhejiang University School of medcine, Hangzhou, China.
Front Pharmacol. 2021 Apr 19;12:653212. doi: 10.3389/fphar.2021.653212. eCollection 2021.
Osteosarcoma is a malignant bone tumor that is easy to metastasize in the early stage and has a very poor prognosis. Fraxinellone (FRA) is one of the main components isolated from the plant. Its anti-inflammatory and neuroprotective effects have been confirmed, but the research on the anti-cancer effect of FRA and its potential mechanism is relatively scarce. In this study, we found that FRA inhibited the proliferation and migration of osteosarcoma cells HOS and MG63 in a dose-dependent manner. Immunofluorescence, fluorescence staining and western blotting analysis showed that FRA could simultaneously induce osteosarcoma cell apoptosis and increase autophagy flux. Subsequent turnaround experiments suggested that the pro-apoptotic effect of FRA was achieved through excessive autophagy flux. The results of the xenograft orthotopic model further supported the anti-cancer effects of FRA, indicating that FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved . These studies provide new ideas for the future treatment of osteosarcoma and offer theoretical support for the anti-cancer mechanism of FRA.
骨肉瘤是一种恶性骨肿瘤，早期易于转移，预后很差。白鲜酮（FRA）是从该植物中分离出的主要成分之一。其抗炎和神经保护作用已得到证实，但关于FRA抗癌作用及其潜在机制的研究相对较少。在本研究中，我们发现FRA以剂量依赖性方式抑制骨肉瘤细胞HOS和MG63的增殖和迁移。免疫荧光、荧光染色和蛋白质印迹分析表明，FRA可同时诱导骨肉瘤细胞凋亡并增加自噬通量。随后的逆转实验表明，FRA的促凋亡作用是通过过度的自噬通量实现的。异种移植原位模型的结果进一步支持了FRA的抗癌作用，表明FRA治疗抑制了骨肉瘤的生长，同时也证实了FRA的促凋亡和自噬作用。这些研究为骨肉瘤的未来治疗提供了新思路，并为FRA的抗癌机制提供了理论支持。
