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Updated: Jun 19, 2026

A Co-culture Method to Investigate the Crosstalk Between X-ray Irradiated Caco-2 Cells and PBMC
Published on: January 30, 2018
TNF-alpha downregulates E-cadherin and sensitizes response to γ-irradiation in Caco-2 cells
Jae Youn Yi1, Yu-Jin Jung, Sun Shim Choi
1Lab of Modulation of Radiobiological Response, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
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 γ-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 γ-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 γ-irradiation. The combined treatment of TNF-alpha with 2 Gy of γ-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 γ-irradiation administered in radiotherapy for the treatment of human colon cancer.
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