Department of Orthopedics, Tumor Hospital Affiliated to Xinjiang Medical University, Xinshi, Urumqi, Xinjiang 830000, P.R. China.
Department of Maternal, Child and Adolescent Health, College of Public Health, Xinjiang Medical University, Xinshi, Urumqi, Xinjiang 830000, P.R. China.
Oncol Rep. 2017 Aug;38(2):933-940. doi: 10.3892/or.2017.5713. Epub 2017 Jun 12.
Osteosarcoma (OS) is a common bone tumor that mainly affects children and young adults. S-phase kinase‑associated protein 2 (Skp2) has been characterized to play a critical oncogenic role in a variety of human malignancies. However, the biological function of Skp2 in OS remains largely obscure. In the present study, we elucidated the role of Skp2 in cell growth, cell cycle, apoptosis and migration in OS cells. We found that depletion of Skp2 inhibited cell growth in both MG-63 and SW 1353 cells. Moreover, we observed that depletion of Skp2 triggered cell apoptosis in two OS cell lines. Furthermore, downregulation of Skp2 induced cell cycle arrest in the G0/G1 phase in OS cells. Notably, our wound healing assay results revealed that inhibition of Skp2 suppressed cell migration in OS cells. Invariably, our western blot results demonstrated that depletion of Skp2 in OS cells inhibited activation of pAkt and increased p27 expression in OS cells, suggesting that Skp2 exerted its oncogenic function partly through the regulation of Akt and p27. Our findings revealed that targeting Skp2 could be a promising therapeutic strategy for the treatment of OS.
骨肉瘤(OS)是一种常见的骨肿瘤,主要影响儿童和青少年。S 期激酶相关蛋白 2(Skp2)已被证实在多种人类恶性肿瘤中发挥关键致癌作用。然而,Skp2 在 OS 中的生物学功能仍很大程度上不清楚。在本研究中,我们阐明了 Skp2 在 OS 细胞中的细胞生长、细胞周期、细胞凋亡和迁移中的作用。我们发现,Skp2 的耗竭抑制了 MG-63 和 SW1353 细胞中的细胞生长。此外,我们观察到 Skp2 的耗竭在两种 OS 细胞系中触发了细胞凋亡。此外,下调 Skp2 在 OS 细胞中诱导细胞周期停滞在 G0/G1 期。值得注意的是,我们的划痕愈合实验结果表明抑制 Skp2 抑制了 OS 细胞的迁移。同样,我们的 Western blot 结果表明,Skp2 在 OS 细胞中的耗竭抑制了 Akt 的激活并增加了 OS 细胞中的 p27 表达,表明 Skp2 通过调节 Akt 和 p27 发挥其致癌功能。我们的研究结果表明,靶向 Skp2 可能是治疗 OS 的一种有前途的治疗策略。