Integrin αvβ3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models

Jeffrey M. Albert, Carolyn Cao, Ling Geng, Lauren Leavitt, Dennis E. Hallahan, Bo Lu

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Purpose: Integrins αvβ3 and αvβ5 are important in tumor growth and angiogenesis and have been recently explored as targets for cancer therapy. Radiotherapy also inhibits tumor growth and affects vasculature. We explored the combination of integrin antagonist Cilengitide (EMD 121974) and ionizing radiation. Methods and Materials: Levels of αvβ3 were determined for human umbilical vein endothelial cells (HUVEC), as well as H157 and H460 human non-small-cell lung cancer cells, using FACS analysis and immunofluorescence imaging. Clonogenic assays, Western immunoblots probed for cleaved caspase 3, and Annexin-V probing were used to evaluate cell survival and apoptosis. A cell detachment assay and matrigel assay were used to further examine the effects of treatment. Results: Human umbilical vein endothelial cells had the highest αvβ3 level, followed by H157, and H460. Interestingly, we found that 5 Gy irradiation induced expression of αvβ3 in all cell lines. Clonogenic assays showed a radiosensitizing effect with Cilengitide, and calculation of the dose enhancement ratio showed that the effect was highest in HUVECs (1.38), followed by H157 (1.19), and H460 (1.10), corresponding to the levels of target expression. There was an increase in apoptotic cells after combination treatment with Cilengitide and radiation, and there was an increase in detached cells after treatment with Cilengitide. Additionally, there was decreased endothelial tubule formation after combination treatment. Conclusions: We conclude that radiation induces expression of αvβ3 integrin in endothelial and non-small-cell lung cancer models, and that integrin antagonist Cilengitide is a radiosensitizer in proportion to the levels of target integrin expression.

Original languageEnglish
Pages (from-to)1536-1543
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume65
Issue number5
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Keywords

  • Cilengitide
  • Endothelial cells
  • Integrin
  • Lung cancer
  • Radiation

Fingerprint Dive into the research topics of 'Integrin α<sub>v</sub>β<sub>3</sub> antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models'. Together they form a unique fingerprint.

  • Cite this