Open Access

Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling

  • Authors:
    • Lu Lu
    • Yuhai Wang
    • Jian Chen
    • Ye Li
    • Qingyang Liang
    • Feng Li
    • Chuanchuan Zhen
    • Kegong Xie
  • View Affiliations

  • Published online on: September 17, 2021     https://doi.org/10.3892/ol.2021.13058
  • Article Number: 797
  • Copyright : © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents and is characterized by early metastasis and frequent recurrence, which greatly affects patient prognosis and survival rates. However, the treatment of OS, its recurrence and subsequent metastasis is now at a clinical bottleneck. To explore new OS chemotherapeutic targets, investigate new therapeutic strategies and improve patient prognosis and survival rates, the roles of paclitaxel (PTX) and monopolar spindle kinase 1 (Mps1) in OS were investigated using in vivo and in vitro models. Mps1 expression was upregulated in OS samples and associated with patient survival times. Moreover, spindle assembly checkpoint (SAC) activation and upregulation of Akt/mTOR signaling were both positively associated with OS progression. PTX treatment significantly inhibited Mps1 expression, as well as migration of OS cells both in vitro. In addition, the combination of Mps1 knockdown and PTX treatment inhibited OS progression in vivo. Mps1 overexpression inhibited the expression of SAC markers and upregulated Akt and mTOR expression, while Mps1 knockdown had the opposite effect. Cells subjected to combined Mps1 knockdown and PTX treatment exhibited activation of SAC and inhibition of Akt/mTOR signaling compared with Mps1 knockdown or PTX treatment alone. Based on these observations, Mps1 inhibition combined with PTX treatment may represent a potentially effective strategy for the treatment of OS.
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November-2021
Volume 22 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Lu L, Wang Y, Chen J, Li Y, Liang Q, Li F, Zhen C and Xie K: Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling. Oncol Lett 22: 797, 2021
APA
Lu, L., Wang, Y., Chen, J., Li, Y., Liang, Q., Li, F. ... Xie, K. (2021). Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling. Oncology Letters, 22, 797. https://doi.org/10.3892/ol.2021.13058
MLA
Lu, L., Wang, Y., Chen, J., Li, Y., Liang, Q., Li, F., Zhen, C., Xie, K."Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling". Oncology Letters 22.5 (2021): 797.
Chicago
Lu, L., Wang, Y., Chen, J., Li, Y., Liang, Q., Li, F., Zhen, C., Xie, K."Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling". Oncology Letters 22, no. 5 (2021): 797. https://doi.org/10.3892/ol.2021.13058