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KMID : 0939920090410030164
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대한암학회지
2009 Volume.41 No. 3 p.164 ~ p.170
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TNF-alpha Downregulates E-cadherin and Sensitizes Response to ?-irradiation in Caco-2 Cells
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Yi Jae-Youn
Jung Yu-Jin
Choi Sun-Shim
Chung Eun-Kyung
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Abstract
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Purpose: The purpose of the present study was to assess the biological effects of TNF-alpha in Caco-2 well-differentiated colon adenocarcinoma cells and to determine radiation sensitivity in order to develop TNF-alpha into a cancer therapeutic agent.
Materials and Methods: A cell viability test was conducted via a colorimetric and colony forming assay after 1 day and 3 days of incubation with TNF-alpha. Western blotting analysis and immunofluorescence staining were conducted to explore TNF-alpha-induced morphological and molecular changes in the adhesion molecules, E-cadherin and claudin-4. The effects of ?-irradiation at a dose of 2 Gy on cell survival were evaluated by a clonogenic assay. The molecular changes in apoptosis-regulatory proteins were assessed by Western blotting.
Results: Caco-2 cells were highly resistant to TNF alpha-induced cell death and 2 Gy of ?-irradiation. However, we observed the downregulation of the adherens junctional protein, E-cadherin and translocation of tight junctional protein, claudin-4 from the membrane to the cytosol induced by TNF-alpha treatment which would indicate cell-cell junction disruptions. These alterations of junctional proteins influenced the regulation of cell death in response to 2 Gy of ?-irradiation. The combined treatment of TNF-alpha with 2 Gy of ?-irradiation reduced the survival of Caco-2 cells by down-regulating bcl-xl and activating JNK pathways.
Conclusion: These results suggest that TNF-alpha might be potentially applied as a therapeutic agent in order to enhance sensitivity to 2 Gy of ?-irradiation administered in radiotherapy for the treatment of human colon cancer.
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KEYWORD
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TNF-alpha, E-cadherin, Claudin-4, Radio-sensitivity, Bcl-xl, Caco-2 cells
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