Department of Orthopaedics, Wuhan Fourth Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
J Biol Regul Homeost Agents. 2020 Sep-Oct;34(5):1699-1708. doi: 10.23812/20-23-A.
Osteosarcoma is the most prevailing malignant bone tumor among adolescents. Punicalagin, a polyphenolic compound extracted from pomegranate, possesses many functions such as anti-oxidation, anti-bacterial, anti-virus, and immunosuppression, which can counter the aggressiveness of a variety of cancers such cervical, ovarian and prostate. This study aimed to investigate the inhibitory effect of punicalagin on the proliferation and metastasis of osteosarcoma cells and its potential regulatory mechanisms. Osteosarcoma cell lines (HOS cells, U2OS cells and MG63 cells) were treated with different doses of punicalagin, and the effects on osteosarcoma cell activity were examined in vitro using cell counting kit-8 (CCK-8), colony formation and apoptosis assays. The mobility, migration and invasion abilities of osteosarcoma cells were detected by wound healing and Transwell assays. NF-κB activity was explored by the NF-κB p65 luciferase reporter assay. Western blot was used to investigate the expressions of downstream proteins. We found that punicalagin inhibited the viability of osteosarcoma cells in vitro in dose-dependent and time-dependent manners and promoted apoptosis. In addition, punicalagin could significantly impede the mobility, migration and invasion abilities of osteosarcoma cells. In terms of mechanism, punicalagin down-regulated the expressions of p65, survivin, XIAP, CIAP2 and other proteins, and suppressed the proliferation and metastasis of osteosarcoma cells by repressing NF-κB signaling pathway. In conclusion, it is concluded that punicalagin restrains the growth and metastasis of osteosarcoma by obstructing the NF-κB signal transduction pathway.
骨肉瘤是青少年中最常见的恶性骨肿瘤。鞣花酸是一种从石榴中提取的多酚化合物，具有抗氧化、抗菌、抗病毒和免疫抑制等多种功能，可抑制宫颈癌、卵巢癌和前列腺癌等多种癌症的侵袭性。本研究旨在探讨鞣花酸对骨肉瘤细胞增殖和转移的抑制作用及其潜在的调节机制。用不同剂量的鞣花酸处理骨肉瘤细胞系（HOS 细胞、U2OS 细胞和 MG63 细胞），并通过细胞计数试剂盒-8（CCK-8）、集落形成和凋亡实验在体外检测对骨肉瘤细胞活性的影响。通过划痕愈合和 Transwell 实验检测骨肉瘤细胞的迁移、迁移和侵袭能力。通过 NF-κB p65 荧光素酶报告基因检测法探讨 NF-κB 活性。通过 Western blot 检测下游蛋白的表达。我们发现，鞣花酸在体外以剂量和时间依赖的方式抑制骨肉瘤细胞的活力，并促进细胞凋亡。此外，鞣花酸可显著抑制骨肉瘤细胞的迁移、迁移和侵袭能力。在机制方面，鞣花酸通过抑制 NF-κB 信号通路下调 p65、survivin、XIAP、CIAP2 等蛋白的表达，抑制骨肉瘤细胞的增殖和转移。总之，鞣花酸通过阻断 NF-κB 信号转导通路抑制骨肉瘤的生长和转移。
