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Updated: Jul 12, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

Targeting integrins and PI3K/Akt-mediated signal transduction pathways enhances radiation-induced anti-angiogenesis

Shoucheng Ning1, Zhijian Chen, Amie Dirks

  • 1Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-5152, USA.

Radiation Research
|August 29, 2007
PubMed

Insights

Combining integrin (cRGD) and PI3K/Akt (LY294002) inhibitors with radiation enhances tumor blood vessel cell death. This radiosensitization strategy targets key pathways in tumor angiogenesis and cell survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Integrins and PI3K/Akt signaling are crucial for tumor angiogenesis and endothelial cell survival post-radiation.
  • Targeting either integrins or PI3K/Akt can sensitize tumors to radiation therapy.

Purpose of the Study:

  • To investigate if combined inhibition of integrin αvβ3 (cRGD) and PI3K/Akt (LY294002) enhances radiation-induced inhibition of vascular endothelial cells.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were treated with cRGD, LY294002, and ionizing radiation.
  • Assessed effects on cell adhesion, tube formation, Akt phosphorylation, COX2 expression, PGE2 production, and apoptosis.

Main Results:

  • cRGD inhibited HUVEC adhesion and tube formation; combined cRGD and LY294002 showed greater inhibition.
  • LY294002 blocked radiation- and cRGD-induced Akt phosphorylation, COX2 upregulation, and increased apoptosis.
  • Combined treatment decreased HUVEC clonogenic survival from 34% (radiation alone) to 4%.

Conclusions:

  • Combined inhibition of integrin αvβ3 and PI3K/Akt synergizes with ionizing radiation.
  • This combination effectively inhibits tumor angiogenesis pathways and enhances radiosensitization of endothelial cells.

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