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Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly

Lu Lu1, Yuhai Wang2, Jian Chen3

  • 1Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.

Oncology Letters
|September 29, 2021
PubMed

Insights

Targeting monopolar spindle kinase 1 (Mps1) with paclitaxel (PTX) shows promise for treating osteosarcoma (OS). This combination therapy inhibits Mps1, reduces OS cell migration, and improves survival rates in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is a common pediatric bone cancer with high rates of metastasis and recurrence.
  • Current OS treatments face clinical limitations, necessitating novel therapeutic targets and strategies.
  • Mps1 (monopolar spindle kinase 1) and its role in OS progression and metastasis require further investigation.

Purpose of the Study:

  • To investigate the roles of paclitaxel (PTX) and Mps1 in osteosarcoma (OS).
  • To explore Mps1 as a potential chemotherapeutic target for OS treatment.
  • To evaluate the efficacy of combining Mps1 inhibition with PTX in OS models.

Main Methods:

  • Utilized in vivo and in vitro models of osteosarcoma.
  • Assessed Mps1 expression levels in OS samples and correlated them with patient survival.
  • Investigated the effects of PTX treatment and Mps1 knockdown, alone and in combination, on OS progression, cell migration, spindle assembly checkpoint (SAC) activation, and Akt/mTOR signaling.

Main Results:

  • Mps1 expression was elevated in OS and linked to poorer patient survival.
  • PTX treatment reduced Mps1 expression and inhibited OS cell migration.
  • Combined Mps1 knockdown and PTX treatment suppressed OS progression in vivo.
  • Mps1 inhibition modulated SAC activation and Akt/mTOR signaling pathways.

Conclusions:

  • Mps1 inhibition, particularly when combined with PTX, demonstrates potential as an effective therapeutic strategy for osteosarcoma.
  • Targeting Mps1 may overcome current treatment bottlenecks for OS, improving patient prognosis.
  • The combination therapy activates the SAC and inhibits Akt/mTOR signaling, offering a novel approach to OS treatment.
Keywords:
Akt/mTOR signalingmonopolar spindle kinase 1osteosarcomapaclitaxelspindle assembly checkpoint

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