Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural protein Nesprin-2 expression in colorectal cancer cells.
Biochim Biophys Acta
; 1840(1): 322-31, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24080406
ABSTRACT
BACKGROUND:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known for treating inflammatory disease and have been reported to have anti-tumorigenic effects. Their mechanisms are not fully understood, but both cyclooxygenase (COX) dependent and independent pathways are involved. Our goal was to shed further light on COX-independent activity.METHODS:
Human colorectal cancer cells were observed under differential interference contrast microscopy (DICM), fluorescent microscopy, and micro-impedance measurement. Microarray analysis was performed using HCT-116 cells treated with sulindac sulfide (SS). PCR and Western blots were performed to confirm the microarray data and immunohistochemistry was performed to screen for Nesprin-2 expression. Micro-impedance was repeating including Nesprin-2 knock-down by siRNA.RESULTS:
HCT-116 cells treated with SS showed dramatic morphological changes under DICM and fluorescent microscopy, as well as weakened cellular adhesion as measured by micro-impedance. Nesprin-2 was selected from two independent microarrays, based on its novelty in relation to cancer and its role in cell organization. SS diminished Nesprin-2 mRNA expression as assessed by reverse transcriptase and real time PCR. Various other NSAIDs were also tested and demonstrated that inhibition of Nesprin-2 mRNA was not unique to SS. Additionally, immunohistochemistry showed higher levels of Nesprin-2 in many tumors in comparison with normal tissues. Further micro-impedance experiments on cells with reduced Nesprin-2 expression showed a proportional loss of cellular adhesion.CONCLUSIONS:
Nesprin-2 is down-regulated by NSAIDs and highly expressed in many cancers. GENERALSIGNIFICANCE:
Our data suggest that Nesprin-2 may be a potential novel oncogene in human cancer cells and NSAIDs could decrease its expression.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Neoplasias Colorretais
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Adesão Celular
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Sulindaco
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Anti-Inflamatórios não Esteroides
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Proteínas dos Microfilamentos
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Proteínas do Tecido Nervoso
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos