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Updated: Jul 1, 2025

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
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Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis

Ping Huang1,2, Lixia Zhang3, Hongwei Wang1,2

  • 1Department of Neurosurgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.

Neuropathology : Official Journal of the Japanese Society of Neuropathology
|March 6, 2024
PubMed

Insights

Neuropilin-1 (NRP-1) enhances glioblastoma cell resistance to temozolomide (TMZ) chemotherapy. Silencing NRP-1 increases TMZ sensitivity by regulating the STAT1/p53/p21 pathway, offering a potential therapeutic target for glioblastoma treatment.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma (GBM) is the most common primary brain tumor.
  • Temozolomide (TMZ) is the standard chemotherapy for GBM.
  • TMZ resistance is a major challenge in GBM treatment.

Purpose of the Study:

  • To investigate the role of neuropilin-1 (NRP-1) in TMZ resistance in GBM.
  • To elucidate the molecular mechanisms underlying NRP-1's effect on TMZ resistance.

Main Methods:

  • Established TMZ-resistant GBM cell lines (U251/TMZ, LN229/TMZ) and a xenograft mouse model.
  • Utilized gene silencing (NRP-1 knockdown) and upregulation techniques.
  • Performed Western blotting, RT-qPCR, and immunohistochemistry to assess protein and mRNA expression.
  • Investigated the STAT1/p53/p21 signaling axis.

Main Results:

  • NRP-1 expression was significantly higher in TMZ-resistant GBM cells.
  • NRP-1 knockdown decreased TMZ resistance in GBM cells and xenograft models.
  • Upregulation of NRP-1 increased TMZ resistance in parental GBM cells.
  • NRP-1 depletion reduced STAT1, p53, and p21 expression.
  • STAT1 knockdown reversed the effect of NRP-1 silencing on TMZ resistance.

Conclusions:

  • NRP-1 plays a crucial role in conferring TMZ resistance in GBM.
  • NRP-1 enhances TMZ resistance potentially through the STAT1/p53/p21 signaling pathway.
  • Targeting NRP-1 may represent a novel therapeutic strategy to overcome TMZ resistance in glioblastoma.
Keywords:
STAT1/p53/p21drug resistanceglioblastoma (GBM)neuropilin‐1(NRP‐1)temozolomide (TMZ)

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