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Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown

Li-Zhi Wu1, You Zou1, Bin-Ru Wang1

  • 1Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, 430060, Hubei, People's Republic of China.

Journal of Translational Medicine
|November 8, 2023
PubMed
Abstract

Insights

Reducing centromere protein N (CENP-N) enhances radiosensitivity in nasopharyngeal carcinoma (NPC) by inhibiting AKT/mTOR. This combined approach significantly suppresses tumor growth and increases apoptosis in NPC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Nasopharyngeal carcinoma (NPC) exhibits variable responses to radiotherapy.
  • Centromere protein N (CENP-N) is a key component of the kinetochore and its role in cancer radiosensitivity is under investigation.
  • Understanding molecular mechanisms influencing NPC radiosensitivity is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the impact of centromere protein N (CENP-N) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells.
  • To explore the potential of targeting CENP-N to enhance radiotherapy efficacy in NPC.

Main Methods:

  • CENP-N expression was assessed in NPC tissues using immunohistochemistry and immunofluorescence.
  • In vitro studies involved CENP-N knockdown combined with radiotherapy, evaluating proliferation, apoptosis, and cell cycle progression.
  • A NPC xenograft model was established to assess the in vivo efficacy of combined CENP-N knockdown and radiotherapy.

Main Results:

  • Lower CENP-N levels correlated with radiosensitive NPC tissues.
  • CENP-N knockdown significantly enhanced NPC radiosensitivity, with Sensitizing Enhancement Ratios (SER) of 1.44 and 1.16.
  • Combined treatment led to increased apoptosis, proliferation suppression, and G2/M arrest, with elevated Bax and γH2AX, and decreased Cyclin D1.
  • In vivo, combined treatment markedly reduced tumor volume and weight compared to radiotherapy alone.
  • AKT activator SC79 reversed the observed effects, suggesting involvement of the AKT/mTOR pathway.

Conclusions:

  • CENP-N knockdown enhances NPC radiosensitivity.
  • The mechanism involves the inhibition of the AKT/mTOR signaling pathway.
  • Targeting CENP-N represents a promising strategy to improve radiotherapy outcomes for nasopharyngeal carcinoma.
Keywords:
AKT/mTOR signaling pathwayApoptosisCENP-NCell cycleNasopharyngeal carcinomaRadiosensitivity

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