Downregulation of CDC20 suppressed cell proliferation, induced apoptosis, triggered cell cycle arrest in osteosarcoma cells, and enhanced chemosensitivity to cisplatin

Yi Gao, Caili Guo, Shuqin Fu,  Yibing Cheng,  Chunlan Song

Abstract:

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.