Thymosin ß10 as a predictive biomarker of response to 5-fluorouracil chemotherapy in cholangiocarcinoma.
Ann Hepatol
; 15(4): 577-85, 2016.
Article
em En
| MEDLINE
| ID: mdl-27236157
ABSTRACT
UNLABELLED Introduction and aim. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic drug in the treatment of cholangiocarcinoma (CCA). Since development of drug resistance to 5-FU in CCA patients is the primary cause of treatment failure, a better understanding of the mechanism of drug resistance of this cancer is essential to improve the efficacy of 5-FU in CCA therapy. MATERIAL AND METHODS:
A 5-FU resistant CCA cell line (M214-5FUR) for a comparative chemo-resistance study was established. Real time RT-PCR was used to determine gene expression levels. Cell cytotoxicity was measured by the MTT assay. Protein expression levels were detected by the immunofluorescene method.RESULTS:
It was found that 5-FU resistance was associated with the overexpression of T?10 in CCA cell lines. 5-FU treatment at various concentrations induced the expressions of T?10 and ABC transporters (ABCB1, ABCG2 ABCA3) in two CCA cell lines, KKU-M055 and KKU-M214. M214-5FUR, a 5-FU-resistant cell line, exhibited a 5-FU resistant phenotype with a 16-fold extremely high expression of T?10 and ABC transporters, as compared to the parental cells, KKU-M214. siRNA targeted to T?10 significantly reduced expression of ABC transporters tested in the M214-5FUR cells (P < 0.05).CONCLUSIONS:
The present novel findingsof T?10 connected with drug resistance as shown in this study provides a new insight for the therapeutic value of T?10 as a predictive biomarker of 5-FU chemoresistance. Inhibiting T?10 may be a valuable adjunct for suppression of ABC transporters and sensitizing chemotherapy treatment, especially 5-FU in CCA patients.
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Base de dados:
MEDLINE
Assunto principal:
Timosina
/
Neoplasias dos Ductos Biliares
/
Biomarcadores Tumorais
/
Colangiocarcinoma
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Transportadores de Cassetes de Ligação de ATP
/
Resistencia a Medicamentos Antineoplásicos
/
Fluoruracila
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Ann Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Tailândia