Gao Yi, Guo Caili, Fu Shuqin, Cheng Yibing, Song Chunlan
Department of Acute and Critical Care Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Zhengzhou Key Laboratory of Critical And Critical Care Medicine for Children, Zhengzhou, China.
Neoplasma. 2021 Mar;68(2):382-390. doi: 10.4149/neo_2020_200614N629. Epub 2020 Oct 30.
Osteosarcoma (OS) is a common malignant bone tumor that occurs in adolescents or children under the age of 20, which is extremely difficult to cure and has a high recurrence rate. Recent studies showed that cell division cycle 20 (CDC20) overexpression is associated with poor prognosis in patients with osteosarcoma. However, the function of CDC20 in osteosarcoma has not been investigated clearly. In this study, we aim to explore the role of CDC20 in two independent human OS cell lines' biological phenotype and chemotherapy sensitivity. We applied multiple approaches to measure cell growth, cell cycle, and apoptosis with or without deregulation or overexpression of CDC20. We found that the downregulation of CDC20 by siRNA or apcin suppressed cell proliferation, induced apoptosis, and triggered cell cycle arrest. Consistently, overexpression of CDC20 in normal cells promoted cell growth, inhibited apoptosis. What's more, the additional treatment with siCDC20 or Apcin achieved better anticancer effects than that of cisplatin alone. Furthermore, Bim and p21 were upregulated in OS cells following Apcin treatment. Altogether, the results of the present study demonstrated that targeting CDC20 could be useful for the treatment of OS, and might be a promising solution for the treatment of the OS with cisplatin insensitivity.
骨肉瘤(OS)是一种常见的恶性骨肿瘤,发生于青少年或20岁以下的儿童,极难治愈且复发率高。最近的研究表明,细胞分裂周期20(CDC20)的过表达与骨肉瘤患者的不良预后相关。然而,CDC20在骨肉瘤中的功能尚未得到明确研究。在本研究中,我们旨在探讨CDC20在两种独立的人OS细胞系的生物学表型和化疗敏感性中的作用。我们应用多种方法来测量在CDC20未受调控或过表达的情况下细胞的生长、细胞周期和凋亡情况。我们发现,通过小干扰RNA(siRNA)或apcin下调CDC20可抑制细胞增殖、诱导凋亡并引发细胞周期停滞。同样,在正常细胞中过表达CDC20可促进细胞生长、抑制凋亡。此外,用siCDC20或apcin进行额外治疗比单独使用顺铂具有更好的抗癌效果。此外,Apcin处理后的OS细胞中Bim和p21上调。总之,本研究结果表明,靶向CDC20可能对骨肉瘤的治疗有用,并且可能是治疗对顺铂不敏感的骨肉瘤的一种有前景的解决方案。