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Measuring Diurnal Rhythms in Autophagic and Proteasomal Flux
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Measuring Diurnal Rhythms in Autophagic and Proteasomal Flux

Published on: September 17, 2019

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Autophagic flux response and glioblastoma sensitivity to radiation

Achilleas G Mitrakas1, Dimitra Kalamida1, Alexandra Giatromanolaki2

  • 1Department of Radiotherapy/Oncology.

Cancer Biology & Medicine
|September 11, 2018
PubMed
Abstract

Insights

Autophagy enhances glioblastoma cell resistance to radiation and chemotherapy. Blocking autophagy, a key factor in glioblastoma, may improve treatment efficacy in patients.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • Glioblastoma is a lethal brain tumor known for resistance to standard treatments.
  • Autophagy plays a role in cancer cell survival and treatment resistance.

Purpose of the Study:

  • To investigate the association between autophagic flux and glioblastoma cell resistance to radiotherapy and chemotherapy.
  • To determine if modulating autophagy can overcome treatment resistance.

Main Methods:

  • Examined autophagy-related protein expression in glioblastoma cells (T98, U87) after irradiation.
  • Investigated the effect of silencing autophagy genes (LC3A, LC3B, TFEB) on glioblastoma cell response to therapy in vitro and in vivo.

Main Results:

  • Radioresistant T98 cells showed increased autophagic flux post-irradiation, while radiosensitive U87 cells had blocked flux.
  • Silencing LC3A, LC3B, and TFEB genes sensitized glioblastoma cells to radiotherapy and temozolomide.
  • LC3A gene silencing enhanced radiation sensitivity in mouse xenografts.

Conclusions:

  • Autophagy is a critical factor in glioblastoma's radio- and chemo-resistance.
  • Targeting autophagy presents a potential strategy to enhance radiochemotherapy efficacy for glioblastoma patients.
Keywords:
GlioblastomaTFEBautophagyradiationtemozolomide

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