Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Mol Med Rep. 2020 Dec;22(6):5191-5198. doi: 10.3892/mmr.2020.11591. Epub 2020 Oct 14.
Oxyresveratrol (ORES) is a natural phenolic compound with multiple biological functions including antioxidation, anti‑inflammation and neuroprotection; however, the inhibitory effect of ORES on osteosarcoma remains largely unknown. The present study aimed to determine the effects of ORES on osteosarcoma cell Saos‑2. Cell Counting Kit‑8 assay was performed to detect Soas‑2 cell viability. Annexin‑FITC/PI staining and JC‑1 staining were used to measure cell apoptosis and the change of mitochondrial membrane potential. In addition, western blotting was conducted to determine the expression levels of apoptotic proteins and the phosphorylation of STAT3. It was found that ORES inhibited cell viability and induced apoptosis of osteosarcoma Saos‑2 cells in a concentration‑dependent manner. In addition, ORES increased the expression levels of apoptotic proteases caspase‑9 and caspase‑3 and reduced mitochondrial membrane potential. In response to ORES treatment, the expression levels of pro‑apoptotic proteins, Bad and Bax, were enhanced, whereas those of anti‑apoptotic proteins, Bcl‑2 and Bcl‑xL, were reduced. In addition, the phosphorylation of STAT3 was attenuated in Saos‑2 cells after treatment with ORES. Inhibition of cell viability and apoptosis induction by ORES were rescued by enhancement of STAT3 activation upon treatment with IL‑6. Collectively, the present study indicated that ORES induced apoptosis and inhibited cell viability, which may be associated with the inhibition of STAT3 activation; thus, ORES represents a promising agent for treating osteosarcoma.
氧代白藜芦醇（ORES）是一种天然酚类化合物，具有多种生物学功能，包括抗氧化、抗炎和神经保护；然而，ORES 对骨肉瘤的抑制作用在很大程度上尚不清楚。本研究旨在确定 ORES 对骨肉瘤细胞 Saos-2 的影响。使用细胞计数试剂盒-8 检测 Saos-2 细胞活力。采用 Annexin-FITC/PI 染色和 JC-1 染色检测细胞凋亡和线粒体膜电位变化。此外，通过蛋白质印迹法测定凋亡蛋白的表达水平和 STAT3 的磷酸化。结果发现，ORES 呈浓度依赖性地抑制骨肉瘤 Saos-2 细胞活力并诱导其凋亡。此外，ORES 增加了凋亡蛋白酶 caspase-9 和 caspase-3 的表达水平，并降低了线粒体膜电位。对 ORES 处理的响应，促凋亡蛋白 Bad 和 Bax 的表达水平增强，而抗凋亡蛋白 Bcl-2 和 Bcl-xL 的表达水平降低。此外，ORES 处理后 Saos-2 细胞中 STAT3 的磷酸化减弱。当用 IL-6 增强 STAT3 激活时，ORES 对细胞活力的抑制和诱导凋亡的作用得到挽救。总之，本研究表明 ORES 诱导凋亡并抑制细胞活力，这可能与抑制 STAT3 激活有关；因此，ORES 可能成为治疗骨肉瘤的一种有前途的药物。
