TNF-alpha Downregulates E-cadherin and Sensitizes Response to gamma-irradiation in Caco-2 Cells.
- Author:
Jae Youn YI
1
;
Yu Jin JUNG
;
Sun Shim CHOI
;
Eunkyung CHUNG
Author Information
1. Lab of Modulation of Radiobiological Response, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
TNF-alpha;
E-cadherin;
Claudin-4;
Radio-sensitivity;
Bcl-xl;
Caco-2 cells
- MeSH:
Adenocarcinoma;
Blotting, Western;
Caco-2 Cells;
Cadherins;
Cell Death;
Cell Survival;
Claudin-4;
Colon;
Colonic Neoplasms;
Cytosol;
Down-Regulation;
Fluorescent Antibody Technique;
Humans;
MAP Kinase Signaling System;
Membranes;
Proteins;
Radiation Tolerance;
Tumor Necrosis Factor-alpha
- From:Cancer Research and Treatment
2009;41(3):164-170
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 gamma-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 gamma-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 gamma-irradiation. The combined treatment of TNF-alpha with 2 Gy of gamma-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 gamma-irradiation administered in radiotherapy for the treatment of human colon cancer.
