Xia J-J, Pei L-B, Zhuang J-P, Ji Y, Xu G-P, Zhang Z-P, Li N, Yan J-L
Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
J Int Med Res. 2010 Jul-Aug;38(4):1294-304. doi: 10.1177/147323001003800411.
Cyclo-oxygenase (COX)-2 inhibitors may exert antitumour effects through COX-2-independent mechanisms. This study investigated the effects of the COX-2 inhibitor celecoxib on the viability of the human osteosarcoma MG-63 cell line and its β-catenin signalling pathway. Cell viability and apoptosis were examined in celecoxib-treated cells or after β-catenin knockdown in vitro. Analyses were performed to detect glycogen synthase kinase (GSK)-3β, phosphorylated GSK-3β, β-catenin, c-Myc and cyclin D1 proteins, and mRNA levels of β-catenin, c-Myc and CCND1 (encoding cyclin D1). β-Catenin was shown to be required for MG63 cell survival and celecoxib exerted an inhibitory effect on the viability of cultured MG-63 cells in a time- and dose-dependent manner. β-Catenin protein decreased in the cytosol and nucleus following celecoxib treatment (from 6 h after initiation of treatment onwards; lowest protein levels were reached at > 72 h). Significant reductions in β-catenin, c-Myc and CCND1 mRNA were observed. Celecoxib inhibited MG-63 cell viability, possibly by activating GSK-3β and inhibiting β-catenin-dependent gene transcription, suggesting a role for celecoxib in osteosarcoma treatment.
环氧化酶（COX）-2抑制剂可能通过非COX-2依赖机制发挥抗肿瘤作用。本研究调查了COX-2抑制剂塞来昔布对人骨肉瘤MG-63细胞系活力及其β-连环蛋白信号通路的影响。在体外对塞来昔布处理的细胞或β-连环蛋白敲低后的细胞进行细胞活力和凋亡检测。进行分析以检测糖原合酶激酶（GSK）-3β、磷酸化GSK-3β、β-连环蛋白、c-Myc和细胞周期蛋白D1蛋白，以及β-连环蛋白、c-Myc和CCND1（编码细胞周期蛋白D1）的mRNA水平。结果显示β-连环蛋白是MG63细胞存活所必需的，塞来昔布对培养的MG-63细胞活力具有时间和剂量依赖性抑制作用。塞来昔布处理后（从处理开始后6小时起；在>72小时时达到最低蛋白水平），β-连环蛋白在细胞质和细胞核中的蛋白水平下降。观察到β-连环蛋白、c-Myc和CCND1 mRNA显著降低。塞来昔布可能通过激活GSK-3β和抑制β-连环蛋白依赖性基因转录来抑制MG-63细胞活力，提示塞来昔布在骨肉瘤治疗中具有一定作用。
