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Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and

Dali Yin1, Norihiko Tamaki, Andrew D Parent

  • 1Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Neurological Research
|April 15, 2005
PubMed
Abstract

Insights

Insulin-like growth factor-I (IGF-I) prevents etoposide-induced apoptosis in glioma cells by upregulating bcl-2 and downregulating CPP32 activity. Blocking IGF-I receptors enhances etoposide

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Chemotherapy resistance in glioma cells is a significant challenge in cancer treatment.
  • Understanding the mechanisms underlying glioma chemoresistance is crucial for developing effective therapies.
  • The role of insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) in glioma apoptosis is not fully elucidated.

Purpose of the Study:

  • To investigate the role of IGF-I and IGF-IR in the apoptotic response of glioma cells to etoposide.
  • To elucidate the molecular mechanisms by which IGF-I influences etoposide-induced apoptosis in glioma.
  • To determine if targeting IGF-IR can overcome chemoresistance in malignant gliomas.

Main Methods:

  • Utilized two human glioma cell lines (U-87MG and KNS-42).
  • Assessed etoposide-induced cell growth inhibition using MTT assays.
  • Evaluated apoptosis via Hoechst staining, DNA fragmentation, and Western blotting.
  • Measured caspase-3 (CPP32) and ICE protease activity using ApoAlert caspase assays.
  • Investigated the effect of IGF-IR antisense on etoposide-treated glioma cells.

Main Results:

  • Etoposide inhibited glioma cell growth and induced apoptosis, increasing wild-type p53 and CPP32 activity.
  • IGF-I significantly reduced etoposide-induced apoptosis by upregulating bcl-2 expression and decreasing CPP32 activity.
  • IGF-IR antisense treatment potentiated the apoptotic effects of etoposide in both cell lines.

Conclusions:

  • IGF-I confers chemoresistance to etoposide in glioma cells through bcl-2 and CPP32 modulation.
  • Inhibition of IGF-IR signaling enhances etoposide-induced apoptosis, suggesting a therapeutic target.
  • The anti-apoptotic effects of IGF-I and IGF-IR are implicated in the chemoresistance of gliomas.

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