Abstract | PURPOSE: METHODS AND MATERIALS: Levels of alpha v beta 3 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 alpha v beta 3 level, followed by H157, and H460. Interestingly, we found that 5 Gy irradiation induced expression of alpha v beta 3 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:
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Authors | Jeffrey M Albert, Carolyn Cao, Ling Geng, Lauren Leavitt, Dennis E Hallahan, Bo Lu |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 65
Issue 5
Pg. 1536-43
(Aug 01 2006)
ISSN: 0360-3016 [Print] United States |
PMID | 16863930
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Integrin alphaVbeta3
- Snake Venoms
- Cilengitide
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Topics |
- Apoptosis
- Carcinoma, Non-Small-Cell Lung
(metabolism, pathology, radiotherapy)
- Cell Line, Tumor
- Combined Modality Therapy
(methods)
- Endothelial Cells
(drug effects, metabolism, radiation effects)
- Endothelium, Vascular
(cytology, metabolism, radiation effects)
- Humans
- Integrin alphaVbeta3
(antagonists & inhibitors, metabolism)
- Lung Neoplasms
(metabolism, pathology, radiotherapy)
- Radiation Tolerance
- Snake Venoms
(therapeutic use)
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