Department of Orthopaedics, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Oncol Rep. 2018 Aug;40(2):841-848. doi: 10.3892/or.2018.6467. Epub 2018 May 30.
Osteosarcoma (OS) is the most common primary malignant bone tumor worldwide, primarily affecting children and adolescents. The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that is activated by its co‑activator Cdc20 during the metaphase‑anaphase transition. Apcin is a novel cell‑permeable molecule that blocks the interaction between APC/C and Cdc20. Cdc20 overexpression has been reported in various malignancies and plays an oncogenic role in tumorigenesis and tumor progression. In the present study, the antitumor properties of apcin, an inhibitor of Cdc20, was investigated in OS cell lines. In addition, the possible molecular target by which apcin mediates cell death was explored. Apcin was demonstrated to inhibit OS cell growth and induce significant apoptosis. The invasion and mobile abilities of OS cells were also markedly suppressed by apcin treatment. Furthermore, Bim and p21 were upregulated in OS cells following apcin treatment. The results of the present study indicated that apcin may have therapeutic potential as a treatment for OS and that Cdc20 may be a promising molecular target for chemotherapy.
骨肉瘤（OS）是世界范围内最常见的原发性恶性骨肿瘤，主要影响儿童和青少年。后期促进复合物/环体（APC/C）是一种泛素连接酶，在中期-后期转化过程中被其共激活因子 Cdc20 激活。Apcin 是一种新型的细胞渗透性分子，可阻断 APC/C 和 Cdc20 之间的相互作用。已报道 Cdc20 在各种恶性肿瘤中过表达，并在肿瘤发生和肿瘤进展中发挥致癌作用。在本研究中，研究了 Cdc20 抑制剂 Apcin 在骨肉瘤细胞系中的抗肿瘤特性。此外，还探讨了 Apcin 介导细胞死亡的可能分子靶标。研究表明，Apcin 可抑制 OS 细胞生长并诱导显著的细胞凋亡。Apcin 处理还显著抑制了 OS 细胞的侵袭和迁移能力。此外，Apcin 处理后 OS 细胞中的 Bim 和 p21 上调。本研究结果表明，Apcin 可能具有作为骨肉瘤治疗的治疗潜力，并且 Cdc20 可能是化疗的有前途的分子靶标。
