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TNF-alpha Downregulates E-cadherin and Sensitizes Response to gamma-irradiation in Caco-2 Cells / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment ; : 164-170, 2009.
Artigo em Inglês | WPRIM | ID: wpr-68318
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Tolerância a Radiação / Adenocarcinoma / Proteínas / Caderinas / Regulação para Baixo / Sobrevivência Celular / Western Blotting / Imunofluorescência / Fator de Necrose Tumoral alfa / Morte Celular Limite: Humanos Idioma: Inglês Revista: Cancer Research and Treatment Ano de publicação: 2009 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Tolerância a Radiação / Adenocarcinoma / Proteínas / Caderinas / Regulação para Baixo / Sobrevivência Celular / Western Blotting / Imunofluorescência / Fator de Necrose Tumoral alfa / Morte Celular Limite: Humanos Idioma: Inglês Revista: Cancer Research and Treatment Ano de publicação: 2009 Tipo de documento: Artigo