Xu Ning, Wang Lili, Fu Shiping, Jiang Bin
Department of Orthopedics, Shanghai Eighth People's Hospital, Shanghai, China.
Department of Oncology, Ninth People's Hospital Affiliated to Medical College of Shanghai Jiaotong University, Shanghai, China.
Arch Med Sci. 2020 Nov 13;17(1):166-176. doi: 10.5114/aoms.2020.100777. eCollection 2021.
Osteosarcoma is the most common primary malignancy of the bone. The existing adjuvant chemotherapy regimens, while improving the overall survival, have been limited by the significant systemic toxicity. Substantial clinical and research efforts are being invested to develop novel pharmaceutical agents. Resveratrol (Res) has been suggested to have a chemopreventive effect. However, the mechanism of Res in osteosarcoma remains to be elucidated.
The MG-63 osteosarcoma cell culture model was used to investigate the chemotherapeutic effect of Res. MTT assay, wound healing assay, and Transwell migration assay were used to document the effect of Res on cell proliferation, migration, and invasion, respectively. Apoptosis in MG-63 cells was quantified with the TUNEL assay. Western blotting analysis was used to examine the molecular changes following Res treatment. Data processing and analysis were conducted using GraphPad Prism 5.0. < 0.05 was considered statistically significant.
Our data suggested that Res blocks cell proliferation, migration, and invasion, and activates apoptotic cell death in osteosarcoma MG-63 cells. We found that Res potentially down-regulates nuclear factor κB (NF-κB) and Akt intracellular signaling transduction. Moreover, the combination of Res and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, resulted in synergistic growth inhibition of osteosarcoma.
Our preclinical study in the MG-63 cell line model supports the translation of Res to the clinical management of patients with osteosarcoma.
骨肉瘤是最常见的原发性骨恶性肿瘤。现有的辅助化疗方案虽然提高了总生存率，但受到显著全身毒性的限制。目前正在投入大量临床和研究工作来开发新型药物。白藜芦醇（Res）已被认为具有化学预防作用。然而，Res在骨肉瘤中的作用机制仍有待阐明。
使用MG-63骨肉瘤细胞培养模型研究Res的化疗效果。MTT法、伤口愈合试验和Transwell迁移试验分别用于记录Res对细胞增殖、迁移和侵袭的影响。用TUNEL法对MG-63细胞中的凋亡进行定量。蛋白质免疫印迹分析用于检测Res处理后的分子变化。使用GraphPad Prism 5.0进行数据处理和分析。P < 0.05被认为具有统计学意义。
我们的数据表明，Res可阻断骨肉瘤MG-63细胞的增殖、迁移和侵袭，并激活凋亡性细胞死亡。我们发现Res可能下调核因子κB（NF-κB）和Akt细胞内信号转导。此外，Res与NF-κB抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）联合使用可导致骨肉瘤生长抑制的协同作用。
我们在MG-63细胞系模型中的临床前研究支持将Res应用于骨肉瘤患者的临床治疗。
